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Yu X, Jin J, Si Y, Zhang H, Song Z. A peptide-based fluorescent bioprobe for EphA2-overexpressing tumor targeting and image-guided surgical resection. Bioorg Med Chem 2025; 120:118090. [PMID: 39904197 DOI: 10.1016/j.bmc.2025.118090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 01/22/2025] [Accepted: 01/25/2025] [Indexed: 02/06/2025]
Abstract
Fluorescence-guided surgery (FGS) is an emerging and highly promising surgical technique in clinic. Owing to its real-time and visual characteristics, it assists in achieving clear pictures on lesion site, tumor boundary and degree of metastasis, which will definitely improve surgery accuracy and minimize cancer recurrence as much as possible. Herein, we report a near-infrared fluorescent bioprobe, YK80, which utilizes a modified heptamethine cyanine dye as the fluorophore and a self-assembling peptide targeting Ephrin receptor A2 (EphA2) proteins as the ligand. The design strategy and the synthetic route to YK80 are described, and then optical properties, pharmacokinetics, binding affinity between YK80 and the protein are further investigated. YK80 shows high affinity (KD ≈ 100 nM) with EphA2-expressing cancer cells and excellent targeting ability in mouse models bearing colorectal tumors. Meanwhile, indocyanine green (ICG), the commonly used non-targeted fluorescent contrast agent is employed as the comparison for in vivo experiments. However, ICG owns no such capability towards cancer cells or solid tumors. Thus, YK80 could potentially serve as a targeted contrast agent for image-guided surgery and this successful example will boost the development of medical imaging, surgical methods as well as translational medicine.
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Affiliation(s)
- Xudong Yu
- Department of Gastroenterology, Yiwu Central Hospital, the Affiliated Yiwu Hospital of Wenzhou Medical University, Yiwu, Zhejiang Province, China.
| | - Jianfei Jin
- Zhejiang Yike Biotech. Co., Ltd, Yiwu, Zhejiang Province, China
| | - Yun Si
- Zhejiang Yike Biotech. Co., Ltd, Yiwu, Zhejiang Province, China
| | - Huanmin Zhang
- Zhejiang Yike Biotech. Co., Ltd, Yiwu, Zhejiang Province, China
| | - Zhegang Song
- Zhejiang Yike Biotech. Co., Ltd, Yiwu, Zhejiang Province, China.
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Campos JL, Suominen S, Pons G, Al-Sakkaf AM, Lusetti IL, Sirota M, Vela FJ, Pires L, Sánchez-Margallo FM, Abellán E, Masiá J. Lymphatic Patterns in the Superficial Circumflex Iliac Artery Perforator Flap. J Reconstr Microsurg 2025; 41:209-218. [PMID: 38848754 PMCID: PMC11825209 DOI: 10.1055/a-2340-9629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 05/22/2024] [Indexed: 06/09/2024]
Abstract
BACKGROUND Lymphedema is a chronic condition, characterized by fluid buildup and tissue swelling and is caused by impairment of the lymphatic system. The lymph interpositional flap transfer technique, in which lymph flow is restored with a flap that includes subdermal lymphatic channels, is an option for surgical reconstruction. The superficial circumflex iliac artery perforator (SCIP) flap can be used for this purpose. This study aimed to describe and characterize the lymphatic patterns within the vascular territory of the SCIP flap. METHODS This cross-sectional multicenter study involved 19 healthy volunteers aged ≥18 years of both sexes assessing the bilateral SCIP flap zone. Superficial lymphatic patterns were evaluated at 4-, 14-, and 24 minutes after indocyanine green (ICG) lymphography injection. Standardized procedures were implemented for all participants in both hospitals. RESULTS The linear pattern was predominant bilaterally. The median number of lymphatic vessels and their length increased over time. Most lymphatic vessels in the SCIP flap were oriented toward the inguinal lymph node (ILN). However, the left SCIP zone lymphatic vessels were directed opposite to the ILN. CONCLUSION The two sides SCIP zones were not significantly different. The primary direction of the bilateral lymphatic vessels was toward the ILN, although only single-side lymphatic vessels were in the opposite direction. These findings emphasize the importance of assessing lymphatic axiality and coherent lymphatic patterns prior to undertaking the SCIP as an interposition flap, to ensure effective restoration of lymphatic flow.
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Affiliation(s)
- José Luis Campos
- Department of Microsurgery, Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain
| | - Sinikka Suominen
- Department of Plastic and Reconstructive Surgery, Helsinki University Central Hospital, Helsinki, Finland
| | - Gemma Pons
- Department of Plastic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Ali M. Al-Sakkaf
- Department of Plastic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Irene Laura Lusetti
- Department of Plastic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Max Sirota
- Department of Plastic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Francisco Javier Vela
- Department of Microsurgery, Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain
| | - Laura Pires
- Department of Microsurgery, Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain
| | | | - Elena Abellán
- Department of Microsurgery, Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain
| | - Jaume Masiá
- Department of Plastic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
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Bou-Samra P, Kennedy GT, Chang A, Guo E, Azari FS, Din A, Santini JT, Bensen ES, Singhal S. Phase 2 Clinical Trial of VGT-309 for Intraoperative Molecular Imaging During Pulmonary Resection. Ann Thorac Surg 2025; 119:625-633. [PMID: 38823756 PMCID: PMC11607179 DOI: 10.1016/j.athoracsur.2024.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/23/2024] [Accepted: 05/06/2024] [Indexed: 06/03/2024]
Abstract
BACKGROUND Advances in intraoperative molecular imaging (IMI) may improve surgical outcomes when resecting tumors in the lung. A single-center trial was conducted using VGT-309, a cathepsin-targeted near-infrared imaging agent that causes lung nodules to fluoresce during surgical resection. The end point of this phase 2 study was to evaluate the frequency that IMI with VGT-309 resulted in a clinically significant event (CSE): localization of pulmonary nodules, discovery of unsuspected additional cancers, or identification of positive margins. METHODS Patients undergoing surgical resection for known or suspected cancer in the lung received VGT-309 (0.32 mg/kg) preoperatively. During the surgical procedure, localization and resection of the nodules were performed using standard surgical techniques. Near-infrared imaging was then used to localize nodules, seek occult lesions, and assess resection margins. Efficacy was measured by the frequency of CSEs. RESULTS Of the 40 patients who underwent pulmonary resection with VGT-309, 17 (42.5%) had at least 1 CSE. Near-infrared imaging identified lesions not found by standard surgical methods in 16 patients, additional cancers not found by preoperative imaging in 1 patient, and margins within 5 mm of the closest staple line in 2 patients. VGT-309 performance was tested across a broad range of tumor types and commercial near-infrared imaging systems. VGT-309 appeared safe, well-tolerated, with no infusion reactions, and no drug-related serious adverse events. CONCLUSIONS This phase 2 study demonstrated the utility of IMI with VGT-309 in localizing pulmonary nodules, recognizing synchronous lesions, and identifying positive margins. A multi-institutional study will further evaluate the efficacy of VGT-309.
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Affiliation(s)
- Patrick Bou-Samra
- Department of Surgery, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania
| | - Gregory T Kennedy
- Department of Surgery, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania
| | - Austin Chang
- Department of Surgery, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania
| | - Emily Guo
- Department of Surgery, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania
| | - Feredun S Azari
- Department of Surgery, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania
| | - Azra Din
- Department of Surgery, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania
| | | | | | - Sunil Singhal
- Department of Surgery, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania.
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De Simone B, Abu-Zidan FM, Boni L, Castillo AMG, Cassinotti E, Corradi F, Di Maggio F, Ashraf H, Baiocchi GL, Tarasconi A, Bonafede M, Truong H, De'Angelis N, Diana M, Coimbra R, Balogh ZJ, Chouillard E, Coccolini F, Kelly MD, Di Saverio S, Di Meo G, Isik A, Leppäniemi A, Litvin A, Moore EE, Pasculli A, Sartelli M, Podda M, Testini M, Wani I, Sakakushev B, Shelat VG, Weber D, Galante JM, Ansaloni L, Agnoletti V, Regimbeau JM, Garulli G, Kirkpatrick AL, Biffl WL, Catena F. Indocyanine green fluorescence-guided surgery in the emergency setting: the WSES international consensus position paper. World J Emerg Surg 2025; 20:13. [PMID: 39948641 PMCID: PMC11823064 DOI: 10.1186/s13017-025-00575-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 01/04/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Decision-making in emergency settings is inherently complex, requiring surgeons to rapidly evaluate various clinical, diagnostic, and environmental factors. The primary objective is to assess a patient's risk for adverse outcomes while balancing diagnoses, management strategies, and available resources. Recently, indocyanine green (ICG) fluorescence imaging has emerged as a valuable tool to enhance surgical vision, demonstrating proven benefits in elective surgeries. AIM This consensus paper provides evidence-based and expert opinion-based recommendations for the standardized use of ICG fluorescence imaging in emergency settings. METHODS Using the PICO framework, the consensus coordinator identified key research areas, topics, and questions regarding the implementation of ICG fluorescence-guided surgery in emergencies. A systematic literature review was conducted, and evidence was evaluated using the GRADE criteria. A panel of expert surgeons reviewed and refined statements and recommendations through a Delphi consensus process, culminating in final approval. RESULTS ICG fluorescence imaging, including angiography and cholangiography, improves intraoperative decision-making in emergency surgeries, potentially reducing procedure duration, complications, and hospital stays. Optimal use requires careful consideration of dosage and timing due to limited tissue penetration (5-10 mm) and variable performance in patients with significant inflammation, scarring, or obesity. ICG is contraindicated in patients with known allergies to iodine or iodine-based contrast agents. Successful implementation depends on appropriate training, availability of equipment, and careful patient selection. CONCLUSIONS Advanced technologies and intraoperative navigation techniques, such as ICG fluorescence-guided surgery, should be prioritized in emergency surgery to improve outcomes. This technology exemplifies precision surgery by enhancing minimally invasive approaches and providing superior real-time evaluation of bowel viability and biliary structures-areas traditionally reliant on the surgeon's visual assessment. Its adoption in emergency settings requires proper training, equipment availability, and standardized protocols. Further research is needed to evaluate cost-effectiveness and expand its applications in urgent surgical procedures.
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Affiliation(s)
- Belinda De Simone
- Department of Emergency and General Minimally Invasive Surgery, Infermi Hospital, AUSL Romagna, Rimini, Italy.
- Department of Theoretical and Applied Sciences, eCampus University, Novedrate, CO, Italy.
| | - Fikri M Abu-Zidan
- Department of Surgery, College of Medicine and Health Sciences, United Arab Emirates University, Al‑Ain, UAE
| | - Luigi Boni
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS - Ca' Granda - Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Ana Maria Gonzalez Castillo
- Emergency Surgery Unit, Department of General Surgery, Pompeu Fabra University, Hospital del Mar, Barcelona, Spain
| | - Elisa Cassinotti
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS - Ca' Granda - Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Francesco Corradi
- Department of Surgical, Medical andMolecularPathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Francesco Di Maggio
- Upper Gastro-Intestinal Surgery Unit, Department of General Surgery, Croydon University Hospital, London, UK
| | - Hajra Ashraf
- Upper Gastro-Intestinal Surgery Unit, Department of General Surgery, Croydon University Hospital, London, UK
| | - Gian Luca Baiocchi
- Unit of General Surgery, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | | | | | - Hung Truong
- Acute Care and Minimally Invasive Surgery, Scripps Memorial Hospital - La Jolla, Green, and Encinitas, La Jolla, USA
| | - Nicola De'Angelis
- Unit of Robotic and Minimally Invasive Digestive Surgery, Ferrara University Hospital, Ferrara, Italy
| | - Michele Diana
- Department of Surgery, University Hospital of Geneva, 1205, Geneva, Switzerland
- ICube Laboratory, Photonics Instrumentation for Health, 67034, Strasbourg, France
| | - Raul Coimbra
- Riverside University Health System Medical Center, Riverside, CA, USA
| | - Zsolt J Balogh
- Department of Traumatology, John Hunter Hospital and University of Newcastle, Newcastle, NSW, Australia
| | - Elie Chouillard
- General Surgery Department, American Hospital of Paris, Paris, France
| | | | | | - Salomone Di Saverio
- General Surgery Unit, Madonna del Soccorso Hospital, AST Ascoli Piceno, San Benedetto del Tronto, Italy
| | - Giovanna Di Meo
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery, University of Bari "A. Moro", Bari, Italy
| | - Arda Isik
- Istanbul Medeniyet University, Istanbul, Turkey
| | - Ari Leppäniemi
- Division of Emergency Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Andrey Litvin
- Department of Surgical Diseases No. 3, Gomel State Medical University, University Clinic, Gomel, Belarus
| | - Ernest E Moore
- Ernest E Moore Shock Trauma Center at Denver Health, University of Colorado, Denver, CO, USA
| | - Alessandro Pasculli
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery, University of Bari "A. Moro", Bari, Italy
| | - Massimo Sartelli
- Department of General Surgery, Macerata Hospital, Macerata, Italy
| | - Mauro Podda
- Department of Surgical Science, Unit of Emergency Surgery, University of Cagliari, Cagliari, Italy
| | - Mario Testini
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery, University of Bari "A. Moro", Bari, Italy
| | - Imtiaz Wani
- Department of Surgery, Government Gousia Hospital, DHS, Srinagar, India
| | - Boris Sakakushev
- General Surgery Department, Medical University, University Hospital St George, Plovdiv, Bulgaria
| | - Vishal G Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Novena, Singapore
| | - Dieter Weber
- Department of General Surgery, Royal Perth Hospital & The University of Western Australia, Perth, Australia
| | - Joseph M Galante
- UC Davis Health, Hospital Clinical Care Services, University of California, Davis, USA
| | - Luca Ansaloni
- Department of General Surgery, University of Pavia, Pavia, Italy
| | - Vanni Agnoletti
- Level 1 Trauma Center, Bufalini Hospital, AUSL Romagna, Cesena, Italy
| | - Jean-Marc Regimbeau
- Service de Chirurgie Digestive du CHU d'Amiens, CHU Sud, Centre Hospitalier Universitaire Amiens-Picardie Site Sud, 80054, Amiens, France
| | - Gianluca Garulli
- Department of Emergency and General Minimally Invasive Surgery, Infermi Hospital, AUSL Romagna, Rimini, Italy
| | - Andrew L Kirkpatrick
- Departments of Surgery and Critical Care Medicine, University of Calgary, Foothills Medical Centre, Calgary, AB, Canada
| | - Walter L Biffl
- Division of Trauma/Acute Care Surgery, Scripps Clinic Medical Group, La Jolla, CA, USA
| | - Fausto Catena
- Department of General and Emergency Surgery, Bufalini Hospital-Level 1 Trauma Center, AUSL Romagna, Cesena, Italy
- Alma Mater Studiorum, University of Bologna, Bologna, Italy
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Yang A, Bai Y, Zhang Y, Xiao R, Zhang H, Chen F, Zeng W. Detection and Treatment with Peptide Power: A New Weapon Against Bacterial Biofilms. ACS Biomater Sci Eng 2025; 11:806-819. [PMID: 39874175 DOI: 10.1021/acsbiomaterials.4c02199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Bacterial biofilms, complex microbial communities encased in a protective extracellular matrix, pose a significant threat to public health due to their inherent antibiotic resistance. This review explores the potential of peptides, particularly antimicrobial peptides (AMPs), as innovative tools to combat biofilm-related infections. AMPs, characterized by their potent antimicrobial activity and tissue permeability, offer a promising approach to overcome the challenges posed by biofilms. By disrupting biofilm architecture, inhibiting bacterial growth, and enhancing biofilm detection through nuclear-based, fluorescence-based, and nanobased techniques, AMPs provide a multifaceted strategy. This review highlights recent advancements, approaches, and strategies in peptide research, examining their potential as both diagnostic and therapeutic agents. It also addresses key challenges and outlines future directions for optimizing peptide-based detection and therapies. By overcoming these challenges and refining peptide design, we can unlock the full potential of AMPs in combating bacterial biofilm infections, paving the way for the development of innovative solutions to tackle biofilm-related diseases and improve global health.
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Affiliation(s)
- Ao Yang
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, P. R. China
| | - Yalin Bai
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, P. R. China
| | - Yuntao Zhang
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, P. R. China
| | - Runsha Xiao
- Xiangya Hospital, Central South University, Changsha 410013, P. R. China
| | - Hanli Zhang
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, P. R. China
| | - Fei Chen
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, P. R. China
| | - Wenbin Zeng
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, P. R. China
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Zherdeva VV, Likhov AR, Saidvaliev UA, Fixler D, Demin D, Volodina VN, Apukhtina UA, Pawar S, Atuar B, Tuchin VV. Enhanced Fluorescence Imaging of Implants Based on Polyester Copolymers in Combination With MRI. JOURNAL OF BIOPHOTONICS 2025:e202400147. [PMID: 39899887 DOI: 10.1002/jbio.202400147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 01/09/2025] [Accepted: 01/12/2025] [Indexed: 02/05/2025]
Abstract
Nowadays, many biodegradable materials are offered for biomedical applications, but there are only a few in vivo methods for their detection and monitoring. In this work, implants based on biodegradable polyester copolymers were labeled with indocyanine green (ICG) for fluorescence imaging in combination with tissue optical clearing (TOC) and magnetic resonance imaging (MRI). The results include in vitro degradation modeling followed by in vivo imaging of copolymer samples that were subcutaneously implanted in BALB/c mice. TOC with 70% glycerol has been demonstrated to significantly improve sample visualization. The TOC efficiency parameter Q demonstrated the variability of effects correlating with the timing of follow-up in the postimplantation period. It has been shown that nonhealing wounds, peri-implantation inflammation, or fibrosis, confirmed by MRI, affect the effectiveness of TOC in the range from Q = -30% to 70%.
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Affiliation(s)
- Victoria V Zherdeva
- Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation
| | - Astemir R Likhov
- Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation
| | - Ulugbek A Saidvaliev
- Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel
| | - Dror Fixler
- Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel
| | - Dmitry Demin
- MIREA - Russian Technological University, Moscow, Russia
| | - Veronika N Volodina
- Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation
| | - Uliana A Apukhtina
- Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation
| | - Shweta Pawar
- Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel
| | - Bar Atuar
- Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel
| | - Valery V Tuchin
- Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation
- Institute of Physics and Science Medical Center, Saratov State University, Saratov, Russian Federation
- Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk State University, Tomsk, Russian Federation
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Pugachev AD, Kozlenko AS, Sazykina MA, Sazykin IS, Rostovtseva IA, Makarova NI, Borodkin GS, Tkachev VV, Utenyshev AN, Demidov OP, Matukhno AE, Ponyatovskaya AM, Azhogina TN, Karchava SK, Klimova MV, Aldoshin SM, Metelitsa AV, Ozhogin IV. Anion and Substituents Effect on Spectral-Kinetic and Biological Characteristics of Spiropyran Salts. Chembiochem 2025; 26:e202400800. [PMID: 39530864 DOI: 10.1002/cbic.202400800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/05/2024] [Accepted: 11/12/2024] [Indexed: 11/16/2024]
Abstract
Spiropyran salts containing a cationic vinyl-3H-indolium moiety are characterized by NIR absorption and fluorescence of their merocyanine forms. This feature makes them promising fluorescent probes and markers for bioimaging. The article focuses on the synthesis and study of the spectral, kinetic and toxic characteristics of such compounds with respect to various substituents in different moieties and the type of anion. A detailed analysis of the acquired data made it possible to draw some important conclusions regarding the influence of structural factors, which will be very useful for the further rational design of such derivatives. In particular, it was shown that the counterion has minimal effect on the spectral and kinetic characteristics of the dyes but dramatically affects the toxicity of the compounds. Following selection of the most appropriate compounds, bioimaging experiments were carried out to visualize planktonic bacteria and bacterial biofilms of E. coli and A. calcoaceticus. The ability to visualize biofilms is critical for the diagnosis of chronic diseases. By the results of molecular docking a theoretical interaction pattern between spiropyran molecules and DNA was proposed.
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Affiliation(s)
- Artem D Pugachev
- Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Anastasiia S Kozlenko
- Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Marina A Sazykina
- Academy of Biology and Biotechnologies, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Ivan S Sazykin
- Academy of Biology and Biotechnologies, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Irina A Rostovtseva
- Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Nadezhda I Makarova
- Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Gennady S Borodkin
- Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Valery V Tkachev
- Laboratory of Structural Chemistry, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry RAS, 1 Ac. Semenov ave., Moscow Region, Chernogolovka, 142432, Russian Federation
| | - Andrei N Utenyshev
- Laboratory of Structural Chemistry, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry RAS, 1 Ac. Semenov ave., Moscow Region, Chernogolovka, 142432, Russian Federation
| | - Oleg P Demidov
- Department of Chemistry, North-Caucasus Federal University, 1 Pushkina str., Stavropol, 355017, Russian Federation
| | - Alexey E Matukhno
- Research Center for Neurotechnology, Southern Federal University, 194 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Arina M Ponyatovskaya
- Research Center for Neurotechnology, Southern Federal University, 194 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Tatiana N Azhogina
- Academy of Biology and Biotechnologies, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Shorena K Karchava
- Academy of Biology and Biotechnologies, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Maria V Klimova
- Academy of Biology and Biotechnologies, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Sergey M Aldoshin
- Laboratory of Structural Chemistry, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry RAS, 1 Ac. Semenov ave., Moscow Region, Chernogolovka, 142432, Russian Federation
| | - Anatoly V Metelitsa
- Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
| | - Ilya V Ozhogin
- Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka ave., Rostov-on-Don, 344090, Russian Federation
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Croft J, Ainsworth G, Corrigan N, Gordon K, Perry A, Twiddy M, Strachan M, Wadsley J, Mehanna H, Sharma N, Glenister E, Stocken DD, Balasubramanian SPP. NIFTy: near-infrared fluorescence (NIRF) imaging to prevent postsurgical hypoparathyroidism (PoSH) after thyroid surgery-a phase II/III pragmatic, multicentre randomised controlled trial protocol in patients undergoing a total or completion thyroidectomy. BMJ Open 2025; 15:e092422. [PMID: 39890139 PMCID: PMC11784174 DOI: 10.1136/bmjopen-2024-092422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 10/30/2024] [Indexed: 02/03/2025] Open
Abstract
INTRODUCTION Postsurgical hypoparathyroidism (PoSH) is an iatrogenic condition that occurs as a complication of several different procedures with thyroid surgery being the most common. PoSH has significant short- and long-term morbidities. The volume of thyroid surgery is increasing, and PoSH is therefore likely to increase. Some studies have shown promising results using near-infrared fluorescence (NIRF) imaging in reducing the risk of PoSH which has the potential to significantly reduce morbidity and costs associated with monitoring and treatment. METHODS AND ANALYSIS NIFTy is an unblinded, parallel group, multicentre, seamless phase II/III randomised controlled trial in patients undergoing total or completion thyroidectomy. The trial incorporates a process evaluation (IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up framework) 2a) to inform the trial protocol, a phase II (IDEAL 2b) analysis using a surrogate primary outcome of 1 day transient hypocalcaemia to determine early futility and phase III (IDEAL 3) assessment of the primary outcome of PoSH at 6 months after surgery. 454 participants will be randomised on a 1:1 basis to evaluate thyroid surgery with NIRF and indocyanine green against standard thyroid surgery in reducing PoSH at 6 months after surgery, with the phase II analysis occurring once data are available for 200 participants. Analysis in both phases will be using multilevel logistic regression incorporating random effects with respect to surgeon and adjusting for minimisation factors. Phase III secondary outcomes include protracted hypoparathyroidism, hypercalcaemia, complications, length of stay, readmissions and patient reported quality of life using the Short Form 36 Health Survey Questionnaire and Hypoparathyroid Patient Questionnaire instruments. ETHICS AND DISSEMINATION NIFTy is funded by National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme (Grant Ref: 17/11/27) and approved by a Research Ethics Committee (reference: 21/WA/0375) and Health Research Authority (HRA). Trial results will be disseminated through conference presentations, peer-reviewed publication and through relevant patient groups. TRIAL REGISTRATION NUMBER ISRCTN59074092.
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Affiliation(s)
- Julie Croft
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Gemma Ainsworth
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Neil Corrigan
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Katie Gordon
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Anna Perry
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Maureen Twiddy
- Institute of Clinical and Applied Health Research, University of Hull, Hull, UK
| | - Mark Strachan
- Consultant Endocrinologist, Metabolic Unit, Western General Hospital, NHS Lothian, Edinburgh, UK
| | | | - Hisham Mehanna
- InHANSE, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
| | | | | | - Deborah D Stocken
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
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9
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Boni L, Cassinotti E, Baldari L. Technique for Laparoscopic Fluorescence-Guided Retroperitoneal Lymph Node Dissection. JAMA Surg 2025:2829513. [PMID: 39878958 DOI: 10.1001/jamasurg.2024.4110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
This Surgical Innovation describes a technique to identify the retroperitoneal lymph using ICG fluorescence, enabling a clear visualization of lymphatics, and nodes that need to be dissected from the surrounding structures.
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Affiliation(s)
- Luigi Boni
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Scienze Cliniche e delle Comunità, University of Milan, Italy
| | - Elisa Cassinotti
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Scienze Cliniche e delle Comunità, University of Milan, Italy
| | - Ludovica Baldari
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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10
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Ritter AS, Poppinga J, Steinkraus KC, Hackert T, Nießen A. Novel Surgical Initiatives in Gastroenteropancreatic Neuroendocrine Tumours. Curr Oncol Rep 2025:10.1007/s11912-024-01632-4. [PMID: 39862354 DOI: 10.1007/s11912-024-01632-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/24/2024] [Indexed: 01/27/2025]
Abstract
PURPOSE OF REVIEW Neuroendocrine tumours (NET) are rare entities arising from hormone producing cells in the gastroentero-pancreatic (GEP) tract. Surgery is the most common treatment of GEP-NETs. RECENT FINDINGS Improvements in surgical techniques allow for more locally advanced and metastasised GEP-NETs to be resected. Laparoscopic and robotically--assisted approaches are increasingly being utilised in the resection of selected GEP-NETs and are facilitated by novel intraoperative tumour localisation tools and parenchyma-sparing methods. At the same time, some authors suggest that indications for formal resections of small well differentiated non-functioning pancreatic NETs and appendiceal NETs should be more restrictive. Advancements in surgery allows for tissue-sparing resections of GEP-NETs. Indications for surgical resection and the extent of the procedure are highly dependent on GEP-NET size, localisation and grading. Robotically assisted surgeries with intraoperative ultrasound and visualisation methods as well as vessel-sparing radical retrograde lymphadenectomies for small intestinal NETs seem to be the future of GEP-NET surgery.
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Affiliation(s)
- Alina S Ritter
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany
| | - Jelte Poppinga
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany
| | - Kira C Steinkraus
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany
| | - Anna Nießen
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany.
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11
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Brezgyte G, Mills M, van Zanten M, Gordon K, Mortimer PS, Ostergaard P. A Systematic Review of Indocyanine Green Lymphography (ICGL) Imaging for the Diagnosis of Primary Lymphoedema. Br J Radiol 2025:tqaf006. [PMID: 39836641 DOI: 10.1093/bjr/tqaf006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 12/18/2024] [Accepted: 01/04/2025] [Indexed: 01/23/2025] Open
Abstract
OBJECTIVES This systematic review aims to evaluate the use of Indocyanine Green Lymphography (ICGL) for the investigation of the lymphatics in the lower limbs of primary lymphoedema patients. METHODS MEDLINE and EMBASE articles from 01/01/2000 to 01/09/2023 were searched for. A total of 11 studies were included in the review after a two-stage screening process. RESULTS Data on patient demographics, ICG contrast injection technique, imaging protocols and imaging outcomes were summarised and reviewed in detail. The review highlights the lack of commonality in protocols used. Factors important for good imaging are highly variable, particularly the number of injections, their location and whether they are delivered intradermally or subcutaneously. CONCLUSIONS ICGL has strong potential to become a diagnostic tool to diagnose lymphoedema, due to its non-ionising nature and cost-effectiveness. However due to the lack of thorough phenotyping and genotyping of patients included in the studies, uncertainty still exists as to the value of the described imaging features such as splash, starburst and diffuse dermal rerouting patterns. Future studies, therefore, should aim to explore the diagnostic utility of ICGL for lymphoedema further through the imaging of primary lymphoedema patients with a confirmed genetic diagnosis and using standardised imaging protocols. ADVANCES IN KNOWLEDGE ICGL is a strong candidate for advancing the diagnosis and understanding of primary lymphoedema, and monitoring response to treatment, but protocol heterogeneity and a lack of consistency in reporting imaging details and patient phenotyping currently hold it back.
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Affiliation(s)
- G Brezgyte
- School of Health & Medical Sciences, City St George's, University of London, London, SW17 0RE, UK
| | - M Mills
- School of Health & Medical Sciences, City St George's, University of London, London, SW17 0RE, UK
| | - M van Zanten
- School of Health & Medical Sciences, City St George's, University of London, London, SW17 0RE, UK
| | - K Gordon
- School of Health & Medical Sciences, City St George's, University of London, London, SW17 0RE, UK
- Lymphovascular Medicine, Dermatology Department, St George's Hospital, Blackshaw Rd, London, SW17 0QT, UK
| | - P S Mortimer
- School of Health & Medical Sciences, City St George's, University of London, London, SW17 0RE, UK
- Lymphovascular Medicine, Dermatology Department, St George's Hospital, Blackshaw Rd, London, SW17 0QT, UK
| | - P Ostergaard
- School of Health & Medical Sciences, City St George's, University of London, London, SW17 0RE, UK
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12
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Al-Jamal WT, Reboredo C, Abdi U, Curci P, Qadadeh R, Alotaibi H, Casettari L, Hatahet T. Biodegradable lipid bilayer-assisted indocyanine green J- aggregates for photothermal therapy: Formulation, in vitro toxicity and in vivo clearance. Int J Pharm 2025; 668:124963. [PMID: 39557180 DOI: 10.1016/j.ijpharm.2024.124963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 09/08/2024] [Accepted: 11/15/2024] [Indexed: 11/20/2024]
Abstract
Indocyanine green (ICG) J-aggregates (IJA) are a unique form of aggregation that exhibits superior properties to monomeric ICG. Despite their higher photoacoustic (PA) signals for imaging and heating stability during photothermal therapy (PTT), they exhibit low stability under a biological milieu. Our group previously proposed a simple procedure for in-situ preparation of IJA into liposomes, accelerating their formation and optical properties. To comprehend their potential applications, we systematically investigated the effect of the lipid bilayer composition on ICG J-aggregation and stability. Moreover, their in vitro compatibility and photothermal toxicity in monolayers and cancer spheroids, besides their in vivo biodistribution and clearance were evaluated. Our findings revealed the importance of high cholesterol and PEG-lipid content and low charged lipids (∼ 5 mol %) in liposomes to promote a high IJA/ICG ratio and, thus, high heating stability. More importantly, IJA-liposomes revealed high biocompatibility in monolayer and cancer spheroids with efficient photothermal toxicity. Finally, IJA-liposomes were cleared from the body without toxicity. Interestingly, IJA-liposomes mainly showed lower affinity to the liver than monomeric ICG, resulting in higher renal clearance. Overall, our biodegradable IJA-liposomes could be an excellent alternative to gold-based agents suitable for PA imaging and cancer PTT.
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Affiliation(s)
- Wafa T Al-Jamal
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, United Kingdom.
| | - Cristian Reboredo
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, United Kingdom
| | - Ubah Abdi
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, United Kingdom
| | - Pia Curci
- School of Pharmacy, Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento n°06, 61029 Urbino, PU, Italy
| | - Raghed Qadadeh
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, United Kingdom
| | - Hamoud Alotaibi
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, United Kingdom; Department of Pharmaceutics, College of Pharmacy, Northern Border University, Arar 91431, Saudi Arabia
| | - Luca Casettari
- School of Pharmacy, Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento n°06, 61029 Urbino, PU, Italy
| | - Taher Hatahet
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, United Kingdom; China Medical University and Queen's University Joint College, Shenyang, People's Republic of China
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13
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Tanev MZ, Tomov GT, Georgiev KG, Georgieva ED, Petkova-Parlapanska KV, Nikolova GD, Karamalakova YD. Evaluation of indocyanine green antimicrobial photodynamic therapy in radical species elimination: an in vitro study. Folia Med (Plovdiv) 2024; 66:876-883. [PMID: 39774359 DOI: 10.3897/folmed.66.e135281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 11/22/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION Antimicrobial photodynamic therapy (aPDT) utilizes light-sensitive materials to inactivate pathogens. Indocyanine green (ICG) is an FDA-approved photosensitizer known for its effective photo-thermal and photo-chemical properties.
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14
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Yamashita A, Jang P, Bao K, Kashiwagi S, Frangioni JV, Choi HS. Indocyanine Blue (ICB) as a Functional Alternative to Indocyanine Green (ICG) for Enhanced 700 nm NIR Imaging. Int J Mol Sci 2024; 25:13547. [PMID: 39769309 PMCID: PMC11676035 DOI: 10.3390/ijms252413547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 12/11/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
Despite significant advancements in bioimaging technology, only a limited number of fluorophores are currently approved for clinical applications. Indocyanine green (ICG) is the first FDA-approved near-infrared (NIR) fluorophore and has significantly advanced clinical interventions over the past three decades. However, its single-channel imaging at 800 nm emission is often insufficient for capturing comprehensive diagnostic information during surgery. In this study, we evaluate indocyanine blue (ICB), an ICG analog with a shorter polymethine bridge, as a promising candidate for multi-channel NIR imaging. ICB demonstrated peak absorption and emission approximately 100 nm shorter than ICG in aqueous solutions, placing it within the 700 nm range of the NIR window. Furthermore, ICB exhibited favorable solubility and optical properties in aqueous environments, supporting its potential for in vivo imaging applications. Notably, ICB shows rapid systemic clearance, likely due to its lower molecular weight, which facilitates clear visualization in angiography, cholangiography, and lymph node mapping with minimal background interference. Additionally, dual-channel imaging of tumors and lymph nodes was achieved using a tumor-targeting fluorophore in conjunction with ICB, illustrating the potential for enhanced intraoperative guidance. ICB emitting at 700 nm, therefore, can be useful in NIR imaging, broadening the possibilities for improved diagnostic accuracy and therapeutic outcomes in clinical settings.
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Affiliation(s)
- Atsushi Yamashita
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Paul Jang
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Kai Bao
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Satoshi Kashiwagi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | | | - Hak Soo Choi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
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15
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Rimereit JE, Lindgren CGW, Nerup N, Madsen GI, Le DQS, Möller S, Qvist N, Ellebaek MB. Incorporating a poly-ε-caprolactone scaffold in a stapled small intestinal anastomosis with induced ischemia significantly increased anastomotic tensile strength. An experimental study in pigs. Scand J Gastroenterol 2024:1-8. [PMID: 39636738 DOI: 10.1080/00365521.2024.2433541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 11/10/2024] [Accepted: 11/17/2024] [Indexed: 12/07/2024]
Abstract
OBJECTIVE Anastomotic leakage is a severe complication with multifactorial aetiology, including impaired tissue oxygenation, infection, inflammation, and anastomotic tension. Reinforcement with poly-ε-caprolactone (PCL) scaffold incorporated in a stapled intestinal anastomosis has demonstrated a significant increase in the anastomotic tensile strength. This study aimed to investigate whether incorporation of the scaffold would influence tensile strength with induced ischemia compared to normal blood perfusion. METHODS Eighteen pigs were randomly allocated into an intervention group with a induced relative reduction in blood perfusion to 30% at the anastomotic area and a control group with normal perfusion controlled by quantitative fluorescence angiography. Each pig recieved two stapled small intestinal anastomoses, one with a PCL scaffold incorporated and one without. On postoperative day five, the anastomoses were subjected to a maximal tensile strength test (MATS) and a histopathological analysis. Tensile strength was measured at three events: when a serosal tear became visible (MATS-1), at transmural rupture (MATS-2), and at maximum load before the load-strain curve dropped (MATS-3). RESULTS In the intervention group, MATS-1 was significantly higher in scaffold-reinforced anastomoses compared to controls (7.9 ± 4.2N and 4.4 ± 2.5N, p < 0.02). The same tendency was found for MATS-2 and MATS-3, with statistically significant differences after adjusting for adhesion grade (p < 0.05). Histological analysis revealed no significant differences in wound healing between groups. CONCLUSION Incorporating a PCL scaffold in a stapled small intestinal anastomosis with induced ischemia improved anastomotic tensile strength.
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Affiliation(s)
- Jon Erlend Rimereit
- Research Unit for Surgery, Odense University Hospital, Odense, Denmark
- University of Southern Denmark, Odense, Denmark
| | - Carl Gunnar William Lindgren
- Research Unit for Surgery, Odense University Hospital, Odense, Denmark
- University of Southern Denmark, Odense, Denmark
| | - Nikolaj Nerup
- Department of Surgical Gastroenterology, Copenhagen University Hospital, Copenhagen, Denmark
| | - Gunvor Iben Madsen
- University of Southern Denmark, Odense, Denmark
- Research Unit for Pathology, Odense University Hospital, Odense, Denmark
| | | | - Sören Möller
- Open Patient Data Explorative Network, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Niels Qvist
- Research Unit for Surgery, Odense University Hospital, Odense, Denmark
- University of Southern Denmark, Odense, Denmark
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16
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Chen P, Varghese P J G, Zhao K, Hu J. Mechanical investigation of a Tandem embolization-visualization system for minimally invasive procedures. J Mech Behav Biomed Mater 2024; 160:106739. [PMID: 39276435 PMCID: PMC11560564 DOI: 10.1016/j.jmbbm.2024.106739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 08/26/2024] [Accepted: 09/11/2024] [Indexed: 09/17/2024]
Abstract
Transcatheter arterial embolization is a minimally invasive intervention process in which the blood supply to a tumor or an abnormal area of tissue is blocked. One of the most commonly used embolic agents in clinics is microsphere (MS). In order to understand the flow behavior of microspheres in arteries, it is essential to study their mechanical properties systematically. In this work, calcium-alginate MSs with varying calcium concentrations were synthesized using a coaxial airflow method. Indocyanine green (ICG) was added as a fluorescent dye. The effect of ICG concentration change on microspheres was investigated by studying morphology, imageability, rheology, and swelling behavior. Then the effect of calcium chloride concentration change on microspheres was studied by conducting rheological tests, atomic force microscopy tests, hemolysis assay, and thrombogenicity assay. Results showed that microspheres with higher ICG concentrations have longer lasting fluorescence and lower storage modulus (G'). Higher concentrations of calcium chloride led to higher G', while the local Young's modulus obtained by AFM test was not significantly affected. The MSs with and without ICG showed good hemocompatibility and thrombogenicity.
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Affiliation(s)
- Peng Chen
- Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC, USA, 27695
| | - George Varghese P J
- Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC, USA, 27695
| | - Keren Zhao
- Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC, USA, 27695
| | - Jingjie Hu
- Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC, USA, 27695.
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17
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Pitsinis V, Kanitkar R, Vinci A, Choong WL, Benson J. Results of a Prospective Randomized Multicenter Study Comparing Indocyanine Green (ICG) Fluorescence Combined with a Standard Tracer Versus ICG Alone for Sentinel Lymph Node Biopsy in Early Breast Cancer: The INFLUENCE Trial. Ann Surg Oncol 2024; 31:8848-8855. [PMID: 39266795 PMCID: PMC11549146 DOI: 10.1245/s10434-024-16176-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 08/27/2024] [Indexed: 09/14/2024]
Abstract
BACKGROUND For clinically node-negative early breast cancer patients, sentinel lymph node biopsy (SLNB) using dual localization with blue dye and radioisotope (RI) is currently standard of care. Documented disadvantages with these tracers have prompted exploration of alternative agents such as fluorescent indocyanine green (ICG), which demonstrates high detection rates combined with other tracers. Results of a randomized study evaluating ICG as a single tracer for SLN identification are presented. METHODS Overall, 100 patients with unilateral, clinically node-negative, biopsy-proven invasive breast cancer (≤5 cm) scheduled for SLNB were recruited in two separate randomized cohorts, with 50 patients receiving ICG alone. Cohort 1 received ICG alone (n = 25) or combined with RI [Technetium99] (n = 25), while Cohort 2 received ICG alone (n = 25) or combined with blue dye (n = 25). The primary outcome was sensitivity for SLN identification. RESULTS Among evaluable patients (n = 97), the overall SLN identification rate was 96.9% (ICG alone = 97.9%; ICG + RI = 100%; ICG + blue dye = 92%). Node positivity rates were 14.9% for ICG alone, 16% for ICG combined with RI, and 20% for ICG combined with blue dye. There were no significant differences (p < 0.05) in performance parameters, with ICG alone being non-inferior to tracer combinations for procedural node positivity rates when adjusted for specific factors. CONCLUSION These results support potential use of ICG as a sole tracer agent for routine SLNB, thereby avoiding disadvantages of RI and/or blue dye. The latter can be safely withheld as a co-tracer without compromising detection of positive nodes in primary surgical patients.
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MESH Headings
- Humans
- Indocyanine Green/administration & dosage
- Female
- Sentinel Lymph Node Biopsy/methods
- Breast Neoplasms/pathology
- Breast Neoplasms/surgery
- Breast Neoplasms/diagnostic imaging
- Middle Aged
- Prospective Studies
- Aged
- Coloring Agents/administration & dosage
- Follow-Up Studies
- Neoplasm Staging
- Sentinel Lymph Node/pathology
- Sentinel Lymph Node/surgery
- Sentinel Lymph Node/diagnostic imaging
- Adult
- Prognosis
- Radiopharmaceuticals
- Carcinoma, Ductal, Breast/surgery
- Carcinoma, Ductal, Breast/pathology
- Carcinoma, Ductal, Breast/diagnostic imaging
- Fluorescence
- Fluorescent Dyes/administration & dosage
- Technetium/administration & dosage
- Neoplasm Invasiveness
- Carcinoma, Lobular/surgery
- Carcinoma, Lobular/pathology
- Carcinoma, Lobular/diagnostic imaging
- Aged, 80 and over
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Affiliation(s)
- Vassilis Pitsinis
- Department of Breast Surgery, NHS Tayside, Dundee, UK.
- Faculty of Medicine, University of Dundee, Dundee, UK.
- , Edinburgh, UK.
| | | | - Alessio Vinci
- Department of Breast Surgery, NHS Tayside, Dundee, UK
- Faculty of Medicine, University of Dundee, Dundee, UK
| | - Wen Ling Choong
- Department of Breast Surgery, NHS Tayside, Dundee, UK
- Faculty of Medicine, University of Dundee, Dundee, UK
| | - John Benson
- Breast Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- School of Medicine, University of Cambridge, Cambridge, UK
- Anglia Ruskin University, Cambridge, UK
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Zhou J, Tan Z, Sun B, Leng Y, Liu S. Application of indocyanine green fluorescence imaging in hepatobiliary surgery. Int J Surg 2024; 110:7948-7961. [PMID: 38884267 PMCID: PMC11634118 DOI: 10.1097/js9.0000000000001802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 05/19/2024] [Indexed: 06/18/2024]
Abstract
Indocyanine green (ICG) is a fluorescent dye with an emission wavelength of about 840 nm, which is selectively absorbed by the liver after intravenous or bile duct injection, and then it is excreted into the intestines through the biliary system. With the rapid development of fluorescence laparoscopy, ICG fluorescence imaging is safe, feasible, and widely used in hepatobiliary surgery. ICG fluorescence imaging is of great significance in precise preoperative and intraoperative localization of liver lesions, real-time visualization of hepatic segmental anatomy, intrahepatic and extrahepatic biliary tract visualization, and liver transplantation. ICG fluorescence imaging facilitates efficient intraoperative hepatobiliary decision-making and improves the safety of minimally invasive hepatobiliary surgery. Advances in imaging systems will increase the use of fluorescence imaging as an intraoperative navigation tool, improving the safety and accuracy of open and laparoscopic/robotic hepatobiliary surgery. Herin, we have reviewed the status of ICG applications in hepatobiliary surgery, aiming to provide new insights for the development of hepatobiliary surgery.
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Affiliation(s)
- Jia Zhou
- Department of Hepatobiliary Surgery/Central Laboratory, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province
- Department of Anesthesiology, The First School of Clinical Medicine, Lanzhou University, Lanzhou
| | - Zhiguo Tan
- Department of Hepatobiliary Surgery/Central Laboratory, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province
- Department of Anesthesiology, The First School of Clinical Medicine, Lanzhou University, Lanzhou
| | - Bo Sun
- Department of Hepatobiliary Surgery/Central Laboratory, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province
- Hunan Engineering Research Center of Digital Hepatobiliary Medicine, Changsha
- Hunan Provincial Key Laboratory of Biliary Disease Prevention and Treatment, Changsha, People’s Republic of China
| | - Yufang Leng
- Department of Anesthesiology, The First School of Clinical Medicine, Lanzhou University, Lanzhou
| | - Sulai Liu
- Department of Hepatobiliary Surgery/Central Laboratory, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province
- Hunan Engineering Research Center of Digital Hepatobiliary Medicine, Changsha
- Hunan Provincial Key Laboratory of Biliary Disease Prevention and Treatment, Changsha, People’s Republic of China
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Rajasinghe M, Lucky T, Kathurusinghe S. The Role of Indocyanine Green With Near-Infrared Imaging for the Intraoperative Detection and Enhancement of Endometriosis Lesions: A Narrative Review. Surg Innov 2024; 31:659-669. [PMID: 39367673 PMCID: PMC11476485 DOI: 10.1177/15533506241290079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/06/2024]
Abstract
Background: There is a clinical need for improved intraoperative detection of endometriosis, and the use of Indocyanine Green with Near-Infrared Imaging (NIR-ICG) is a novel technique for this purpose. The aim of this review is to determine whether NIR-ICG is an effective tool for endometriosis detection and establish an evidence-based methodology for its use.Methods: This review searches Ovid MEDLINE and Embase through July 2023 and considers primary literature published in English describing the use of NIR-ICG to detect endometriosis intraoperatively. Case studies, video demonstrations and articles describing NIR-ICG used for other surgical roles were not considered. Identified studies were screened independently by two authors, and data was extracted by a single author.Results: NIR-ICG was found to enhance the detection of endometriosis in six out of the nine included studies with additional lesion identification, and to have an unchanged or reduced efficacy compared to current standards in the remaining three. Across all studies there were lesions missed by NIR-ICG which were detected by conventional imaging. A greater duration of time between dye administration and visualisation of lesions was found to be more effective for detection. The ideal ICG protocol proposed from this review is a fixed amount of dye proportional to patient weight prior to surgery (0.25-0.3 mg/kg) followed by a longer waiting time before imaging (10-30 min).Conclusion: NIR-ICG has a possible role to enhance the identification of endometriosis intraoperatively as an adjunct to conventional white light imaging, particularly deeper infiltrating disease. However, substantial further research is required in this field.
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Affiliation(s)
- Minoli Rajasinghe
- Epworth Healthcare, Richmond, VIC, Australia
- Faculty of Medicine, Dentistry & Health Sciences, University of Melbourne, Melbourne, VIC, Australia
| | - Tarana Lucky
- Epworth Healthcare, Richmond, VIC, Australia
- Faculty of Medicine, Dentistry & Health Sciences, University of Melbourne, Melbourne, VIC, Australia
- Gynaecology, Royal Women’s Hospital, Melbourne, VIC, Australia
| | - Shamitha Kathurusinghe
- Epworth Healthcare, Richmond, VIC, Australia
- Faculty of Medicine, Dentistry & Health Sciences, University of Melbourne, Melbourne, VIC, Australia
- Gynaecology, Royal Women’s Hospital, Melbourne, VIC, Australia
- Gynaecology, Eastern Health, Melbourne, VIC, Australia
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20
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Patel J, Kalikar V, Patankar R, Supe A. Is Indocyanine Green the New Gold Standard for Checking Completion of Laparoscopic Heller's Cardiomyotomy? Cureus 2024; 16:e75344. [PMID: 39781145 PMCID: PMC11707402 DOI: 10.7759/cureus.75344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2024] [Indexed: 01/12/2025] Open
Abstract
Achalasia cardia is a primary motility disorder of the esophagus marked by the absence of peristalsis and the failure of the lower esophageal sphincter (LES) to relax during swallowing. The preferred surgical approach is laparoscopic Heller's cardiomyotomy with Dor's fundoplication. Given the significant risks of mucosal perforation and the possibility of incomplete myotomy, which can lead to symptom recurrence, it is essential to ensure both the completeness of the myotomy and the preservation of the mucosal integrity. In this study, we present a case series of 15 patients diagnosed with achalasia cardia who underwent laparoscopic Heller's cardiomyotomy with Dor's fundoplication. Intraoperatively, we utilized intraluminal administration of indocyanine green (ICG) dye as an alternative to endoscopy to assess the completeness of the myotomy and to check for any mucosal perforations.
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Affiliation(s)
- Jainil Patel
- Department of Surgery, Zen Hospital, Mumbai, IND
| | | | | | - Avinash Supe
- Department of Surgery, Zen Hospital, Mumbai, IND
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21
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Vig S, Gaitan B, Frankle L, Chen Y, Elespuru R, Pfefer TJ, Huang HC. Test method for evaluating the photocytotoxic potential of fluorescence imaging products. Photochem Photobiol 2024; 100:1561-1578. [PMID: 37496175 DOI: 10.1111/php.13836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/23/2023] [Accepted: 06/26/2023] [Indexed: 07/28/2023]
Abstract
Various fluorescence imaging agents are currently under clinical studies. Despite significant benefits, phototoxicity is a barrier to the clinical translation of fluorophores. Current regulatory guidelines on medication-based phototoxicity focus on skin effects during sun exposure. However, with systemic and local administration of fluorophores and targeted illumination, there is now possibility of photochemical damage to deeper tissues during intraoperative imaging procedures. Hence, independent knowledge regarding phototoxicity is required to facilitate the development of fluorescence imaging products. Previously, we studied a cell-free assay for initial screening of reactive molecular species generation from fluorophores. The current work addresses a safety test method based on cell viability as an adjunct and a comparator with the cell-free assay. Our goal is to modify and implement an approach based on the in vitro 3T3 neutral red uptake assay of the Organization for Economic Co-Operation and Development Test Guideline 432 (OECD TG432) to evaluate the photocytotoxicity of clinically relevant fluorophores. These included indocyanine green (ICG), proflavine, methylene blue (MB), and IRDye800, as well as control photosensitizers, benzoporphyrin derivative (BPD) and rose bengal (RB). We performed measurements at agent concentrations and illumination parameters used for clinic imaging. Our results aligned with prior studies, indicating photocytotoxicity in RB and BPD and an absence of reactivity for ICG and IRDye800. DNA interactive agents, proflavine and MB, exhibited drug/light dose-response curves like photosensitizers. This study provides evidence and insights into practices useful for testing the photochemical safety of fluorescence imaging products.
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Affiliation(s)
- Shruti Vig
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
| | - Brandon Gaitan
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
- Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA
| | - Lucas Frankle
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
| | - Yu Chen
- Department of Biomedical Engineering, University of Massachusetts, Amherst, Massachusetts, USA
| | - Rosalie Elespuru
- Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA
| | - T Joshua Pfefer
- Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA
| | - Huang-Chiao Huang
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA
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22
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Manavi MA, Salehi M, Mohammad Jafari R, Dehpour AR. From dyes to drugs: The historical impact and future potential of dyes in drug discovery. Arch Pharm (Weinheim) 2024; 357:e2400532. [PMID: 39239985 DOI: 10.1002/ardp.202400532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 08/15/2024] [Accepted: 08/16/2024] [Indexed: 09/07/2024]
Abstract
In the late 19th century, progress in dye chemistry led to advances in industrial organic chemistry in Germany. Over the next few decades, this revealed dyes not just as color agents but as promising lead compounds for drug development. Collaborations between dye chemists and medical researchers were crucial in turning these unexpected discoveries into structured medicinal chemistry efforts. The outcomes included major drug classes like sulfa antibiotics, antifungal azoles, and others, resulting in a legacy where dyes served not only as biological stains but as crucial tools for understanding complex natural products and drug interactions. Today, the impact of dye molecules persists in clinical therapies, molecular probing, pharmacokinetic tracing, and high-throughput screening. This review underscores the historical contributions shaping contemporary pharmaceutical sciences, highlighting the role of dyes as indispensable tools propelling drug discovery across generations.
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Affiliation(s)
- Mohammad Amin Manavi
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Salehi
- Research Center for antibiotic stewardship and antimicrobial resistance, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Department of Infectious Disease and Tropical Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Razieh Mohammad Jafari
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Reza Dehpour
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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23
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Chauvet P, Jacobs A, Jaillet L, Comptour A, Pereira B, Canis M, Bourdel N. Indocyanine green in gynecologic surgery: Where do we stand? A literature review and meta-analysis. J Gynecol Obstet Hum Reprod 2024; 53:102819. [PMID: 38950735 DOI: 10.1016/j.jogoh.2024.102819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 06/28/2024] [Indexed: 07/03/2024]
Abstract
The main objective of this study was to review and perform a meta-analysis of current literature on the use of indocyanine green for sentinel lymph node detection in pelvic gynecologic cancer. We included all studies focusing on indications and procedures associated with the use of ICG in gynecologic surgery and available on the Medline and Pubmed database. For the meta-analysis, random effect models were used for estimation of the 95 % detection rate and 95 % confidence interval, and stratified analyses by cancer type, concentration and localization of injection were performed. A total of 147 articles were included, of which 91 were studied in a meta-analysis. Results concerning detection rate by indocyanine green injection site were found to be 95.1 % and 97.3 % respectively for intracervical injection in 2 or 4 quadrants, and 77.0 % and 94.8 % for hysteroscopic and intradermal injection respectively. Results concerning detection rate by cancer type were 95.8 %, 95.2 %, 94.7 % and 95.7 % respectively for cervical, endometrial, vulvar and endometrial/cervical cancers. Finally, the results concerning detection rate by indocyanine green concentration were 91.2 %, 95.7 %, 96.7 % and 97.7 % for concentrations of <1.25 mg/ml, 1.25 mg/ml, 2.5 mg/ml and 5 mg/ml respectively. In conclusion, indocyanine green is shown to allow highlighting of sentinel lymph nodes with good reliability with an overall indocyanine green detection rate of 95.5 %. Our literature review revealed that indocyanine green feasibility has also been demonstrated in several surgical contexts, notably for reconstructive surgery and detection of endometriosis.
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Affiliation(s)
- Pauline Chauvet
- CHU Clermont-Ferrand, Department of Gynecologic surgery, CHU Estaing, 1 Place Lucie et Raymond Aubrac, 63000 Clermont, Ferrand, France; Université Clermont Auvergne, EnCoV, Institut Pascal, UMR 6602 CNRS, SIGMA Clermont, F-63000 Clermont, Ferrand, France; INSERM, CIC 1405 CRECHE Unit, CHU Clermont-Ferrand, Department of Gynecological Surgery, 63000 Clermont, Ferrand, France.
| | - Aurélie Jacobs
- CHU Clermont-Ferrand, Department of Gynecologic surgery, CHU Estaing, 1 Place Lucie et Raymond Aubrac, 63000 Clermont, Ferrand, France; INSERM, CIC 1405 CRECHE Unit, CHU Clermont-Ferrand, Department of Gynecological Surgery, 63000 Clermont, Ferrand, France
| | - Lucie Jaillet
- CHU Clermont-Ferrand, Department of Gynecologic surgery, CHU Estaing, 1 Place Lucie et Raymond Aubrac, 63000 Clermont, Ferrand, France; Université Clermont Auvergne, EnCoV, Institut Pascal, UMR 6602 CNRS, SIGMA Clermont, F-63000 Clermont, Ferrand, France
| | - Aurélie Comptour
- CHU Clermont-Ferrand, Department of Gynecologic surgery, CHU Estaing, 1 Place Lucie et Raymond Aubrac, 63000 Clermont, Ferrand, France; INSERM, CIC 1405 CRECHE Unit, CHU Clermont-Ferrand, Department of Gynecological Surgery, 63000 Clermont, Ferrand, France
| | - Bruno Pereira
- CHU Clermont-Ferrand, Biostatistics Unit, 7 Place Henri Dunant, 63000 Clermont, Ferrand, France
| | - Michel Canis
- CHU Clermont-Ferrand, Department of Gynecologic surgery, CHU Estaing, 1 Place Lucie et Raymond Aubrac, 63000 Clermont, Ferrand, France; Université Clermont Auvergne, EnCoV, Institut Pascal, UMR 6602 CNRS, SIGMA Clermont, F-63000 Clermont, Ferrand, France; INSERM, CIC 1405 CRECHE Unit, CHU Clermont-Ferrand, Department of Gynecological Surgery, 63000 Clermont, Ferrand, France
| | - Nicolas Bourdel
- CHU Clermont-Ferrand, Department of Gynecologic surgery, CHU Estaing, 1 Place Lucie et Raymond Aubrac, 63000 Clermont, Ferrand, France; Université Clermont Auvergne, EnCoV, Institut Pascal, UMR 6602 CNRS, SIGMA Clermont, F-63000 Clermont, Ferrand, France; INSERM, CIC 1405 CRECHE Unit, CHU Clermont-Ferrand, Department of Gynecological Surgery, 63000 Clermont, Ferrand, France
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24
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Essang S, Greer A. Shades of phototoxicity in fluorescent imaging agents (that are not supposed to be phototoxic). Photochem Photobiol 2024; 100:1694-1697. [PMID: 37698338 DOI: 10.1111/php.13856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 08/27/2023] [Accepted: 08/29/2023] [Indexed: 09/13/2023]
Abstract
This article is a highlight of the paper by Huang et al. in this issue of Photochemistry and Photobiology. It describes shades of phototoxicity in fluorescent imaging agents that are not intended to be phototoxic. Phototoxicity was assessed using a modified neutral red uptake (NRU) in vitro assay with mean photo-effects (MPE) for the fluorescent agents IRdye800, indocyanine green (ICG), proflavine, and methylene blue (MB), with comparisons to known phototoxic agents benzoporphyrin derivative (BPD) and rose bengal (RB). The experimental conditions were aimed to mimic clinical settings, using not only visible light, but also near-infrared light for insight to photosafety and deep tissue damage. Molecular mechanisms underlying the phototoxicities were not sought, but IRdye800 and ICG were mainly deemed to be safe, whereas proflavine and MB would require precautions since phototoxicity can overshadow their utility as fluorescent imaging agents.
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Affiliation(s)
- Serah Essang
- Department of Chemistry, Brooklyn College of the City University of New York, Brooklyn, New York, USA
- Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York, USA
| | - Alexander Greer
- Department of Chemistry, Brooklyn College of the City University of New York, Brooklyn, New York, USA
- Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York, USA
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25
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Murata T, Tsutsui H, Shiina I. ( E)-Selective Weinreb Amide-Type Horner-Wadsworth-Emmons Reaction: Effect of Reaction Conditions, Substrate Scope, Isolation of a Reactive Magnesium Phosphonoenolate, and Applications. J Org Chem 2024; 89:15414-15435. [PMID: 39393081 PMCID: PMC11536377 DOI: 10.1021/acs.joc.4c01140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 08/07/2024] [Accepted: 09/12/2024] [Indexed: 10/13/2024]
Abstract
An iPrMgCl-deprotonating Weinreb amide-type Horner-Wadsworth-Emmons (HWE) reaction was developed, and the effects of diverse reaction conditions, including the base, cation, solvent, and concentration, were investigated to broaden the substrate scope and achieve high (E)-selectivity. The Weinreb amide-type phosphonoenolate generated from iPrMgCl was found to be isolable, stable for at least over a half year, and applicable in the HWE reaction keeping high productivity and selectivity compared with the in situ generated phosphonoenolate. The results prompted us to perform an application study including successive elongation, synthesis of a biscyclopropane, and Weinreb ketone syntheses.
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Affiliation(s)
| | | | - Isamu Shiina
- Department of Applied Chemistry,
Faculty of Science, Tokyo University of
Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
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26
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Bradbury NC, Li BY, Allen T, Caram JR, Neuhauser D. No more gap-shifting: Stochastic many-body-theory based TDHF for accurate theory of polymethine cyanine dyes. J Chem Phys 2024; 161:141101. [PMID: 39377322 DOI: 10.1063/5.0223783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 08/15/2024] [Indexed: 10/09/2024] Open
Abstract
We introduce an individually fitted screened-exchange interaction for the time-dependent Hartree-Fock (TDHF) method and show that it resolves the missing binding energies in polymethine organic dye molecules compared to time-dependent density functional theory (TDDFT). The interaction kernel, which can be thought of as a dielectric function, is generated by stochastic fitting to the screened-Coulomb interaction of many-body perturbation theory (MBPT), specific to each system. We test our method on the flavylium and indocyanine green dye families with a modifiable length of the polymethine bridge, leading to excitations ranging from visible to short-wave infrared. Our approach validates earlier observations on the importance of inclusion of medium range exchange for the exciton binding energy. Our resulting method, TDHF@vW, also achieves a mean absolute error on a par with MBPT at a computational cost on a par with local-functional TDDFT.
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Affiliation(s)
- Nadine C Bradbury
- Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA
| | - Barry Y Li
- Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA
| | - Tucker Allen
- Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA
| | - Justin R Caram
- Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA
| | - Daniel Neuhauser
- Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA
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27
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Cossu G, Le Van T, Kerherve L, Houidi SA, Morlaix E, Bonneville F, Chapon R, Baland O, Cao C, Lleu M, Farah W, El Cadhi A, Beaurain J, Picart T, Xu B, Berhouma M. Enlightening the invisible: Applications, limits and perspectives of intraoperative fluorescence in neurosurgery. BRAIN & SPINE 2024; 4:103928. [PMID: 39823065 PMCID: PMC11735926 DOI: 10.1016/j.bas.2024.103928] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 10/08/2024] [Accepted: 10/09/2024] [Indexed: 01/19/2025]
Abstract
Introduction The introduction of intraoperative fluorophores represented a significant advancement in neurosurgical practice. Nowadays they found different applications: in oncology to improve the visualization of tumoral tissue and optimize resection rates and in vascular neurosurgery to assess the exclusion of vascular malformations or the permeability of bypasses, with real-time intraoperative evaluations. Research question A comprehensive knowledge of how fluorophores work is crucial to maximize their benefits and to incorporate them into daily neurosurgical practice. We would like to revise here their applications and clinical relevance. Material and methods A focused literature review of relevant articles dealing with the versatile applications of fluorophores in neurosurgery was performed. Results The fundamental mechanisms of action of intraoperative fluorophores are enlightened, examining their interactions with target tissues and the principles driving fluorescence-guided surgery. The clinical applications of the principal fluorophores, namely fluorescein sodium, 5-ALA and indocyanine green, are detailed, in regards to the management of vascular malformations, brain tumors and pathologies treated through endoscopic endonasal approaches. Discussion and conclusion Future perspective dealing with the development of new technologies or of new molecules are discussed. By critically assessing the efficacy and applications of the different fluorophores, as well as charting their potential future uses, this paper seeks to guide clinicians in their practice and provide insights for driving innovation and progress in fluorescence-based surgery and research.
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Affiliation(s)
- Giulia Cossu
- Department of Neurosurgery, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Tuan Le Van
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Luc Kerherve
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Sayda A. Houidi
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Edouard Morlaix
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Florent Bonneville
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Renan Chapon
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Olivier Baland
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Catherine Cao
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Maxime Lleu
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Walid Farah
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Ahmed El Cadhi
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Jacques Beaurain
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
| | - Thiebaud Picart
- Department of Neurosurgery, Groupe Hospitalier Est, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France
- Université Claude Bernard Lyon 1, 43 Bd du 11 Novembre 1918, Villeurbanne, France
- Cancer Research Centre of Lyon (CRCL), INSERM 1052, CNRS 5286, 28 Rue Laennec, Lyon, France
| | - Bin Xu
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Moncef Berhouma
- Department of Neurosurgery, University Hospital of Dijon Bourgogne, Dijon, France
- Functional and Molecular Imaging Team (CNRS 6302), Molecular Chemistry Institute (ICMUB), University of Burgundy, France
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28
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Carbonell E, Sierra A, Mercader C, Peradejordi M, Muní M, Tello A, Alfambra H, Martínez C, Ajami T, Izquierdo L, Vilaseca A, Ribal MJ, Alcaraz A, Martos R, Musquera M. Intravenous indocyanine green to evaluate distal ureteral vascularity during robot-assisted radical cystectomy with intracorporeal urinary diversion. World J Urol 2024; 42:568. [PMID: 39379730 DOI: 10.1007/s00345-024-05284-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 09/20/2024] [Indexed: 10/10/2024] Open
Abstract
PURPOSE The aim of the present study is to assess the role of indocyanine green (ICG) to evaluate distal ureteral vascularity during robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion and its impact on the incidence of benign ureteroenteric strictures (UES). METHODS The study included patients who underwent RARC for bladder cancer between 2018 and 2023. All patients included underwent intracorporeal urinary diversion with ileal conduit or neobladder. Bricker technique was performed in all ureteroenteric anastomosis. ICG was employed during the study period to evaluate ureteral vascularity. We divided patients into 2 groups depending on the utilization of ICG during surgery and compared demographic, clinicopathological and perioperative outcomes, including benign UES rates. RESULTS We identified 221 patients that underwent RARC with intracorporeal urinary diversion. Ileal conduit was performed in 173 (78.3%) patients and neobladder in 48 (21.7%) cases. A total of 142 (64.3%) and 79 (35.7%) patients were in the non-ICG and ICG group, respectively. With a median follow-up of the entire cohort of 21.1 months, there were no differences in the rate of benign UES after RARC between the non-ICG and the ICG group (p = 0.901). In the non-ICG group, 26 (18.3%) patients developed benign UES and in the ICG group 15 (19.0%) patients. Most of the strictures appeared in the left ureter in both groups (80.8% non-ICG vs. 66.7% ICG, p = 0.599). Median time to stricture diagnosis was 4 months (IQR 3-7.25) for the non-ICG and 3 months (IQR 2-5) for the ICG group (p = 0.091). The ICG group had a slightly greater length of ureter resected compared with the non-ICG group (1.5 vs. 1.3 cm, p = 0.007). CONCLUSION In our experience, choosing to use ICG intraoperatively to evaluate distal ureteral vascularity may not reduce the rate of benign UES after robot-assisted radical cystectomy with intracorporeal urinary diversion and Bricker ureteroileal anastomosis.
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Affiliation(s)
- Enric Carbonell
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Alba Sierra
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Clàudia Mercader
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain.
| | - Mònica Peradejordi
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Maria Muní
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Alberto Tello
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Héctor Alfambra
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Carmen Martínez
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Tarek Ajami
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Laura Izquierdo
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Antoni Vilaseca
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - María José Ribal
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Antonio Alcaraz
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Raúl Martos
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
| | - Mireia Musquera
- Department of Urology, Hospital Clínic de Barcelona, Villarroel 170, Barcelona, 08036, Spain
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29
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Verma N, Setia A, Mehata AK, Randhave N, Badgujar P, Malik AK, Muthu MS. Recent Advancement of Indocyanine Green Based Nanotheranostics for Imaging and Therapy of Coronary Atherosclerosis. Mol Pharm 2024; 21:4804-4826. [PMID: 39225111 DOI: 10.1021/acs.molpharmaceut.4c00495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Atherosclerosis is a vascular intima condition in which any part of the circulatory system is affected, including the aorta and coronary arteries. Indocyanine green (ICG), a theranostic compound approved by the FDA, has shown promise in the treatment of coronary atherosclerosis after incorporation into nanoplatforms. By integration of ICG with targeting agents such as peptides or antibodies, it is feasible to increase its concentration in damaged arteries, hence increasing atherosclerosis detection. Nanotheranostics offers cutting-edge techniques for the clinical diagnosis and therapy of atherosclerotic plaques. Combining the optical properties of ICG with those of nanocarriers enables the improved imaging of atherosclerotic plaques and targeted therapeutic interventions. Several ICG-based nanotheranostics platforms have been developed such as polymeric nanoparticles, iron oxide nanoparticles, biomimetic systems, liposomes, peptide-based systems, etc. Theranostics for atherosclerosis diagnosis use magnetic resonance imaging (MRI), computed tomography (CT), near-infrared fluorescence (NIRF) imaging, photoacoustic/ultrasound imaging, positron emission tomography (PET), and single photon emission computed tomography (SPECT) imaging techniques. In addition to imaging, there is growing interest in employing ICG to treat atherosclerosis. In this review, we provide a conceptual explanation of ICG-based nanotheranostics for the imaging and therapy of coronary atherosclerosis. Moreover, advancements in imaging modalities such as MRI, CT, PET, SPECT, and ultrasound/photoacoustic have been discussed. Furthermore, we highlight the applications of ICG for coronary atherosclerosis.
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Affiliation(s)
- Nidhi Verma
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Aseem Setia
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Abhishesh Kumar Mehata
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Nandini Randhave
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Paresh Badgujar
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Ankit Kumar Malik
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India
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30
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Fadel MG, Zonoobi E, Rodríguez-Luna MR, Mishima K, Ris F, Diana M, Vahrmeijer AL, Perretta S, Ashrafian H, Fehervari M. Efficacy and Safety of Fluorescence-Guided Surgery Compared to Conventional Surgery in the Management of Colorectal Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2024; 16:3377. [PMID: 39409997 PMCID: PMC11476237 DOI: 10.3390/cancers16193377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/09/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND The use of fluorescence agents and imaging systems is a promising adjunct in the surgical management of colorectal cancer. This systematic review and meta-analysis aimed to assess the safety and efficacy of fluorescence-guided surgery in the management of colorectal cancer, with a comparison to conventional (non-fluorescence-guided) surgery. METHODS A literature search of MEDLINE, Embase, Emcare, and CINAHL databases was performed for studies that reported data on the outcomes of fluorescence-guided surgery, with or without a comparison group undergoing conventional surgery, for colorectal cancer between January 2000 and January 2024. A meta-analysis was performed using random-effect models, and between-study heterogeneity was assessed. RESULTS 35 studies of 3217 patients with colorectal cancer were included: 26 studies (964 patients) reported on fluorescence-guided surgery and 9 studies (2253 patients) reported on fluorescence versus conventional surgery. The weighted mean of the cancer detection rate of fluorescence-guided surgery was 71% (95% CI 0.55-0.85), with no significant difference in lymph node yield ratio (WMD -0.04; 95% CI -0.10-0.02; p = 0.201) between fluorescence and conventional surgery groups. There was a significantly lower blood loss (WMD -4.38; 95% CI -7.05--1.70; p = 0.001) and complication rate (WMD -0.04; 95% CI -0.07-0.00; p = 0.027) in the fluorescence-guided surgery group, with a potentially lower anastomotic leak rate (WMD -0.05; 95% CI -0.10-0.01; p = 0.092). CONCLUSIONS Fluorescence-guided surgery is a safe and effective approach in the management of colorectal cancer, potentially reducing blood loss and complications. Further randomised controlled trials are required comparing fluorescence-guided surgery with conventional surgery to determine its prognostic benefit and where it should precisely fit within the management pathway of colorectal cancer.
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Affiliation(s)
- Michael G. Fadel
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
- Department of General Surgery, Chelsea and Westminster Hospital, London SW10 9NH, UK
| | - Elham Zonoobi
- Edinburgh Molecular Imaging Limited, Nine Edinburgh Bioquarter, Edinburgh EH16 4UX, UK
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | | | - Kohei Mishima
- Research Institute Against Digestive Cancer (IRCAD), 67000 Strasbourg, France
| | - Frédéric Ris
- Department of Surgery, University Hospital of Geneva, 1205 Geneva, Switzerland
- Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
| | - Michele Diana
- Department of Surgery, University Hospital of Geneva, 1205 Geneva, Switzerland
- Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
- ICube Laboratory, Photonics Instrumentation for Health, 67034 Strasbourg, France
| | | | - Silvana Perretta
- Research Institute Against Digestive Cancer (IRCAD), 67000 Strasbourg, France
- IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France
- Department of Digestive and Endocrine Surgery, University of Strasbourg, 67081 Strasbourg, France
| | - Hutan Ashrafian
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
| | - Matyas Fehervari
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
- Department of Gastrointestinal Surgery, Maidstone and Tunbridge Wells NHS Trust, Tunbridge Wells TN2 4QJ, UK
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31
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Tange FP, van den Hoven P, van Schaik J, Schepers A, van der Bogt KEA, van Rijswijk CSP, Putter H, Vahrmeijer AL, Hamming JF, van der Vorst JR. Near-Infrared Fluorescence Imaging With Indocyanine Green to Predict Clinical Outcome After Revascularization in Lower Extremity Arterial Disease. Angiology 2024; 75:884-892. [PMID: 37358400 PMCID: PMC11375904 DOI: 10.1177/00033197231186096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2023]
Abstract
Contemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the potential of near-infrared fluorescence imaging with indocyanine green to predict the clinical outcome following revascularization. Near-infrared fluorescence imaging was performed before and within 5 days following the revascularization procedure. Clinical improvement was defined as substantial improvement of pain free walking distance, reduction of rest- and/or nocturnal pain, or tendency toward wound healing. Time-intensity curves and 8 perfusion parameters were extracted from the dorsum of the treated foot. The quantified postinterventional perfusion improvement was compared within the clinical outcome groups. Successful near-infrared fluorescence imaging was performed in 72 patients (76 limbs, 52.6% claudication, 47.4% chronic limb-threatening ischemia) including 40 endovascular- and 36 surgical/hybrid revascularizations. Clinical improvement was observed in 61 patients. All perfusion parameters showed a significant postinterventional difference in the clinical improvement group (P-values <.001), while no significant differences were seen in the group without clinical improvement (P-values .168-.929). Four parameters demonstrated significant differences in percentage improvement comparing the outcome groups (P-values within .002-.006). Near-infrared fluorescence imaging has promising additional value besides clinical parameters for predicting the clinical outcome of revascularized LEAD patients.
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Affiliation(s)
- Floris P Tange
- Department of Surgery, Leiden University Medical Center, The Netherlands
| | - Pim van den Hoven
- Department of Surgery, Leiden University Medical Center, The Netherlands
| | - Jan van Schaik
- Department of Surgery, Leiden University Medical Center, The Netherlands
| | - Abbey Schepers
- Department of Surgery, Leiden University Medical Center, The Netherlands
| | | | | | - Hein Putter
- Department of Medical Statistics, Leiden University Medical Center, The Netherlands
| | | | - Jaap F Hamming
- Department of Surgery, Leiden University Medical Center, The Netherlands
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32
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Moukarzel LA, Andres S, Zivanovic O. The use of near-infrared angiography in evaluating bowel anastomosis during a gynecologic oncology surgery. Gynecol Oncol Rep 2024; 55:101474. [PMID: 39252761 PMCID: PMC11381474 DOI: 10.1016/j.gore.2024.101474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 07/23/2024] [Accepted: 07/26/2024] [Indexed: 09/11/2024] Open
Abstract
Reducing anastomotic leak rates after bowel resection is a priority among patients undergoing gynecologic oncology surgery. While near-infrared (NIR) angiography has been investigated in the colorectal literature, more recent work has demonstrated promising results when used in gynecologic cancer surgery. It has been repeatedly shown to be a safe intervention that can offer real time assessment of bowel perfusion, offering the surgeon the opportunity to act on the results in the hopes of decreasing the risk of complications.
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Affiliation(s)
- Lea A. Moukarzel
- Department of Obstetrics and Gynecology, Asplundh Cancer Pavilion of Sidney Kimmel Cancer Center, Jefferson Abington Hospital, Abington, PA, USA
| | - Sarah Andres
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Oliver Zivanovic
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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33
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Sasaki M, Murata Y. Anaphylaxis induced by indocyanine green during abdominal surgery: A case report. Saudi J Anaesth 2024; 18:590-592. [PMID: 39600445 PMCID: PMC11587973 DOI: 10.4103/sja.sja_260_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 05/05/2024] [Indexed: 11/29/2024] Open
Abstract
Since 2011, indocyanine green (ICG) has been increasingly used in surgery as a diagnostic tool. Although allergic reactions to this fluorescent dye are considered rare, they can result in anaphylactic shock. We report the case of a 33-year-old woman who developed anaphylaxis immediately after ICG administration during laparoscopic-assisted high anterior resection. The patient was treated with intravenous adrenaline, and the surgery continued. Elevated plasma histamine and serum tryptase levels immediately after ICG administration and intradermal testing identified ICG as the causative agent. The frequency of ICG use is increasing, and anesthesiologists should recognize ICG as a prevalent perioperative allergen.
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Affiliation(s)
- Momoko Sasaki
- Department of Anesthesiology, University of Tsukuba Hospital, Tsukuba, Japan
| | - Yuya Murata
- Department of Anesthesiology, University of Tsukuba Hospital, Tsukuba, Japan
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34
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Villa A, Crescenti D, De Mitri Z, Crippa E, Rosa S, Rizzi N, Shojaei-Ghahrizjani F, Rebecchi M, Vincenti S, Selmin F, Brunialti E, Simonotti N, Maspero M, Dei Cas M, Recordati C, Paltrinieri S, Giordano A, Paroni R, Galassi M, Ladisa V, Arienti F, Cilurzo F, Mazzaferro V, Ciana P. Preclinical pharmacology of patient-derived extracellular vesicles for the intraoperative imaging of tumors. Theranostics 2024; 14:6301-6318. [PMID: 39431003 PMCID: PMC11488097 DOI: 10.7150/thno.98671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 08/14/2024] [Indexed: 10/22/2024] Open
Abstract
Extracellular vesicles (EVs) derived from the plasma of oncological patients exhibit significant tumor-targeting properties, unlike those from healthy individuals. We have previously shown the feasibility of formulating the near-infrared (NIR) fluorescent dye indocyanine green (ICG) with patient-derived extracellular vesicles (PDEVs) for selective delivery to neoplastic tissue. This staining protocol holds promise for clinical application in intraoperative tumor margin imaging, enabling precise neoplastic tissue resection. To this end, we propose the ONCOGREEN protocol, involving PDEV isolation, ICG loading, and reinfusion into the same patients. Methods: By in vivo studies on mice, we outlined key pharmacological parameters of PDEVs-ICG for intraoperative tumor imaging, PDEV biodistribution kinetics, and potential treatment-related toxicological effects. Additionally, we established a plasmapheresis-based protocol for isolating autologous PDEVs, ensuring the necessary large-scale dosage for human treatment. A potential lyophilization-based preservation method was also explored to facilitate the storage and transport of PDEVs. Results: The study identified the effective dose of PDEVs-ICG necessary for clear intraoperative tumor margin imaging. The biodistribution kinetics of PDEVs showed favorable targeting to neoplastic tissues, without off-target distribution. Toxicological assessments revealed no significant adverse effects associated with the treatment. The plasmapheresis-based isolation protocol successfully yielded a sufficient quantity of autologous PDEVs, and the lyophilization preservation method maintained the functional integrity of PDEVs for subsequent clinical application. Conclusions: Our research lays the groundwork for the direct clinical application of autologous PDEVs, initially focusing on intraoperative imaging. Utilizing autologous PDEVs has the potential to accelerate the integration of EVs as a targeted delivery tool for anti-neoplastic agents to cancerous tissue. This approach promises to enhance the precision of neoplastic tissue resection and improve overall surgical outcomes for oncological patients.
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Affiliation(s)
- Alessandro Villa
- Department of Health Sciences, University of Milan, Milan, Italy
| | | | - Zemira De Mitri
- Department of Health Sciences, University of Milan, Milan, Italy
| | | | - Silvia Rosa
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Nicoletta Rizzi
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | | | - Monica Rebecchi
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Simona Vincenti
- Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Francesca Selmin
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | | | - Nicolò Simonotti
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Marianna Maspero
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Michele Dei Cas
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Camilla Recordati
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Milan, Italy
| | - Saverio Paltrinieri
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Milan, Italy
| | - Alessia Giordano
- Department of Veterinary Medicine and Animal Sciences, University of Milan, Milan, Italy
| | - Rita Paroni
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Margherita Galassi
- HPB Surgery and Liver Transplantation, Istituto Nazionale Tumori IRCCS Foundation (INT), Milan, Italy
| | - Vito Ladisa
- HPB Surgery and Liver Transplantation, Istituto Nazionale Tumori IRCCS Foundation (INT), Milan, Italy
| | - Flavio Arienti
- HPB Surgery and Liver Transplantation, Istituto Nazionale Tumori IRCCS Foundation (INT), Milan, Italy
| | - Francesco Cilurzo
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | - Vincenzo Mazzaferro
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
- HPB Surgery and Liver Transplantation, Istituto Nazionale Tumori IRCCS Foundation (INT), Milan, Italy
| | - Paolo Ciana
- Department of Health Sciences, University of Milan, Milan, Italy
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35
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Siddiqua A, Clutter E, Garklavs O, Kanniyappan H, Wang RR. Electrospun Silk-ICG Composite Fibers and the Application toward Hemorrhage Control. J Funct Biomater 2024; 15:272. [PMID: 39330247 PMCID: PMC11433354 DOI: 10.3390/jfb15090272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/07/2024] [Accepted: 09/13/2024] [Indexed: 09/28/2024] Open
Abstract
In trauma and surgery, efficient hemorrhage control is crucial to avert fatal blood loss and increase the likelihood of survival. There is a significant demand for novel biomaterials capable of promptly and effectively managing bleeding. This study aimed to develop flexible biocomposite fibrous scaffolds with an electrospinning technique using silk fibroin (SF) and indocyanine green (ICG). The FDA-approved ICG dye has unique photothermal properties. The water permeability, degradability, and biocompatibility of Bombyx mori cocoon-derived SF make it promising for biomedical applications. While as-spun SF-ICG fibers were dissolvable in water, ethanol vapor treatment (EVT) effectively induced secondary structural changes to promote β-sheet formation. This resulted in significantly improved aqueous stability and mechanical strength of the fibers, thereby increasing their fluid uptake capability. The enhanced SF-ICG interaction effectively prevented ICG leaching from the composite fibers, enabling them to generate heat under NIR irradiation due to ICG's photothermal properties. Our results showed that an SF-ICG 0.4% fibrous matrix can uptake 473% water. When water was replaced by bovine blood, a 25 s NIR irradiation induced complete blood coagulation. However, pure silk did not have the same effect. Additionally, NIR irradiation of the SF-ICG fibers successfully stopped the flow of blood in an in vitro model that mimicked a damaged blood vessel. This novel breakthrough offers a biotextile platform poised to enhance patient outcomes across various medical scenarios, representing a significant milestone in functional biomaterials.
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Affiliation(s)
- Ayesha Siddiqua
- Department of Chemistry, Illinois Institute of Technology, Chicago, IL 60616, USA
| | - Elwin Clutter
- Department of Chemistry, Illinois Institute of Technology, Chicago, IL 60616, USA
| | - Olga Garklavs
- Wilbur Wright College, City Colleges of Chicago, Chicago, IL 60634, USA
| | | | - Rong R Wang
- Department of Chemistry, Illinois Institute of Technology, Chicago, IL 60616, USA
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Zhao X, Du J, Sun W, Fan J, Peng X. Regulating Charge Transfer in Cyanine Dyes: A Universal Methodology for Enhancing Cancer Phototherapeutic Efficacy. Acc Chem Res 2024; 57:2582-2593. [PMID: 39152945 DOI: 10.1021/acs.accounts.4c00399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2024]
Abstract
ConspectusDue to the advantages of spatiotemporal selectivity and inherent noninvasiveness, cancer phototherapy, which includes both photodynamic therapy (PDT) and photothermal therapy (PTT), has garnered significant attention in recent years as a promising cancer treatment. Despite the commendable progress in this field, persistent challenges remain. In PDT, limitations in dyes manifest as low intersystem crossing (ISC) efficiency and oxygen-dependent photoactivity, resulting in unsatisfactory performance, particularly under hypoxic conditions. Similarly, PTT encounters consistent insufficiencies in the photothermal conversion efficiency (PCE) of dyes. Additionally, the suboptimal phototherapeutic efficacy often exhibits a limited immune response. These factors collectively impose significant constraints on phototherapy in oncological applications, leading to limited tumor inhibition, tumor recurrence, and even metastasis.Unlike strategies that rely on external assistance with complicated systems, manipulating excited-state deactivation pathways in biocompatible dyes offers a universal way to systematically address these challenges. Our group has devoted considerable effort to achieving this goal. In this Account, we present and discuss our journey in optimizing excited-state energy-release pathways through regulating molecular charge transfer based on cyanine dyes, which are renowned for their exceptional photophysical properties and harmonious biocompatibility. The investigation begins with the introduction of amino groups in the meso position of a heptamethine cyanine dye, where the intramolecular charge transfer (ICT) effect causes a significant enlargement of the Stokes shift. Subsequently, ICT induced by introducing functional electron-deficient groups in cyanines is found to decrease the overlap of electron distribution or narrow the energy gaps of molecular frontier orbitals. Such modifications result in a reduction of the energy gaps between singlet and triplet states or an improvement in internal conversion, ultimately promoting phototherapy efficacy in both primary and distant tumors. Furthermore, with the intensification of the charge transfer effect aided by light, photoinduced intramolecular electron transfer occurs in some cyanines, leading to complete charge separation in the excited state. This process enhances the transition to the ground or triplet states, improving tumor phototherapy and inhibiting metastasis by increasing the PCE or the yield of reactive oxygen species, respectively. Shifting focus from intramolecular to intermolecular interactions, we successfully constructed and explored cyanines based on intermolecular charge transfer. These dyes, with excited-state dynamics mimicking natural photosynthesis, generate radicals and facilitate oxygen-independent hypoxic tumor PDT. Finally, we outlined the existing challenges and future directions for optimizing phototherapeutic efficacy by regulating molecular charge transfer. This Account provides molecular-level insights into improving phototherapeutic performance, offering valuable perspectives, and inspiring the development of functional dyes in other application fields.
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Affiliation(s)
- Xueze Zhao
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, No. 2 Linggong Road, 116024 Dalian, China
- Department of Chemistry, The University of Hong Kong, Hong Kong SAR 999077, China
| | - Jianjun Du
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, No. 2 Linggong Road, 116024 Dalian, China
| | - Wen Sun
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, No. 2 Linggong Road, 116024 Dalian, China
| | - Jiangli Fan
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, No. 2 Linggong Road, 116024 Dalian, China
- Ningbo Institute of Dalian University of Technology, No. 26 Yucai Road, 315016 Ningbo, China
| | - Xiaojun Peng
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, No. 2 Linggong Road, 116024 Dalian, China
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Raimondo D, Raffone A, Aguzzi A, Bertoldo L, Seracchioli R. Role of sentinel lymph node biopsy with indocyanine green and site of injection in endometrial cancer. Curr Opin Oncol 2024; 36:383-390. [PMID: 39106403 DOI: 10.1097/cco.0000000000001075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/09/2024]
Abstract
PURPOSE OF REVIEW The aim of the present narrative review is to summarize the state of art on sentinel lymph node biopsy (SLNB) in endometrial cancer, with a special focus on indocyanine green (ICG) as adopted tracer. RECENT FINDINGS Over the years, the surgical nodal staging in patients with endometrial cancer has been intensively investigated. Traditionally, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess nodal involvement of the tumor. Through the last two decades, SLNB has gradually replaced lymphadenectomy as a more targeted procedure. A great heterogeneity of tracers and injection techniques have been proposed to perform SLNB. However, no universally accepted recommendations are still available. SUMMARY SLNB has nowadays almost replaced pelvic lymphadenectomy in low-risk endometrial cancers, offering a better safety profile while being related to a comparable nodal involvement sensitivity. Currently, ICG is considered to be the most used tracer among others. Different injection sites have been proposed, with different detection features. While ICG cervical injection is nowadays the suggested technique for SLNB, noncervical injection techniques, such as hysteroscopic and combined procedures, seem to have a better accuracy in para-aortic nodal assessment, which have a role in high-risk endometrial cancers.
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Affiliation(s)
- Diego Raimondo
- Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
| | - Antonio Raffone
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Alberto Aguzzi
- Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna
| | - Linda Bertoldo
- Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna
| | - Renato Seracchioli
- Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna
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Bindu A, Kumar V, Kulkarni OS, Jaiswal D, Mathews S, Mantri M, Mokhale K, Shankhdhar VK. Flow-Through Radial Artery Forearm Flap for Tongue Revascularization After Excision of Base of Tongue Malignancies. Indian J Surg Oncol 2024; 15:478-483. [PMID: 39239434 PMCID: PMC11372037 DOI: 10.1007/s13193-024-01929-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 03/18/2024] [Indexed: 09/07/2024] Open
Abstract
Tongue cancers are common in the spectrum of oral malignancies. In base of tongue cancers, tumour excision might lead to injury of ipsilateral or both lingual arteries, leading to ischemia of residual, native tongue. Free radial artery forearm flap is commonly used for tongue reconstruction. It can also be used as a flow-through flap for the reconstruction of the tongue defect as well as to revascularise the cancer-free tongue remnant. We report here two cases of base of tongue excision for which free flow-through radial forearm flap was used to reconstruct the tongue defect as well as salvage the remaining part of ischemic tongue. This technique can be effectively considered in selected cases of vascular compromise due to lingual vessel sacrifice to preserve the cancer-free anterior native tongue tissue with improved functional outcomes.
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Affiliation(s)
- Ameya Bindu
- Department of Plastic and Reconstructive Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Parel, Mumbai, 400012 Maharashtra India
| | - Vineet Kumar
- Department of Plastic and Reconstructive Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Parel, Mumbai, 400012 Maharashtra India
| | - Onkar S. Kulkarni
- Department of Plastic and Reconstructive Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Parel, Mumbai, 400012 Maharashtra India
| | - Dushyant Jaiswal
- Department of Plastic and Reconstructive Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Parel, Mumbai, 400012 Maharashtra India
| | - Saumya Mathews
- Department of Plastic and Reconstructive Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Parel, Mumbai, 400012 Maharashtra India
| | - Mayur Mantri
- Department of Plastic and Reconstructive Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Parel, Mumbai, 400012 Maharashtra India
| | - Kunal Mokhale
- Department of Plastic and Reconstructive Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Parel, Mumbai, 400012 Maharashtra India
| | - Vinay Kant Shankhdhar
- Department of Plastic and Reconstructive Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E. Borges Road, Parel, Mumbai, 400012 Maharashtra India
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39
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Christofi A, Traska T, Dimitroulis D. Near-infrared indocyanine green angiography in recognizing bowel ischemia in emergency surgery: game changer or overrated? Innov Surg Sci 2024; 9:113-121. [PMID: 39309192 PMCID: PMC11415940 DOI: 10.1515/iss-2024-0013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 06/21/2024] [Indexed: 09/25/2024] Open
Abstract
Assessing bowel perfusion in emergency intestinal surgery can prove challenging even for experienced surgeons. The necessity of a technological tool assisting clinicians is undisputed. Near-infrared indocyanine green (NIR-ICG) angiography has been increasingly used in elective colorectal surgery to evaluate intestinal perfusion with promising results. This review aims to answer whether a similar outcome can be observed in acute cases of bowel ischemia. We conducted online research of the literature using keywords such as "indocyanine green", "bowel", "emergency" and "ischemia", to identify articles concerning the use of ICG-angiography in evaluating bowel perfusion during emergency operations. PubMed was the primary database. 11 articles were included in this systematic review with a total of 358 patients. Most papers showed a positive effect after using NIR-ICG-angiography, whereas one study indicated the limitations of the method by exhibiting increased reoperation and mortality rates. Moreover, a significant variation in indocyanine green (ICG) dose and fluorescence identification systems was observed. NIR-ICG-angiography has the potential to become a fundamental tool in emergency intestinal operations. Nevertheless, additional research, especially high-quality, randomized studies, as well as quantification techniques are still needed to support these preliminary observations.
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Affiliation(s)
- Anastasia Christofi
- Department of General, Visceral and Vascular Surgery, Agaplesion Bethesda Hospital Wuppertal, Wuppertal, Germany
- Hellenic Minimally Invasive and Robotic Surgery (MIRS) Study Group, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Thilo Traska
- Department of General, Visceral and Vascular Surgery, Agaplesion Bethesda Hospital Wuppertal, Wuppertal, Germany
| | - Dimitrios Dimitroulis
- Hellenic Minimally Invasive and Robotic Surgery (MIRS) Study Group, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Second Department of Propedeutic Surgery, Laiko Hospital, Athens, Greece
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40
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Nishimura G, Suzuki T, Yamada Y, Niwa H, Koike T. Depth detection limit of a fluorescent object in tissue-like medium with background emission in continuous-wave measurements: a phantom study. JOURNAL OF BIOMEDICAL OPTICS 2024; 29:097001. [PMID: 39224540 PMCID: PMC11368132 DOI: 10.1117/1.jbo.29.9.097001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 07/10/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024]
Abstract
Significance Although the depth detection limit of fluorescence objects in tissue has been studied, reports with a model including noise statistics for designing the optimum measurement configuration are missing. We demonstrate a variance analysis of the depth detection limit toward clinical applications such as noninvasively assessing the risk of aspiration. Aim It is essential to analyze how the depth detection limit of the fluorescence object in a strong scattering medium depends on the measurement configuration to optimize the configuration. We aim to evaluate the depth detection limit from theoretical analysis and phantom experiments and discuss the source-detector distance that maximizes this limit. Approach Experiments for detecting a fluorescent object in a biological tissue-mimicking phantom of ground beef with background emission were conducted using continuous wave fluorescence measurements with a point source-detector scheme. The results were analyzed using a model based on the photon diffusion equations. Then, variance analysis of the signal fluctuation was introduced. Results The model explained the measured fluorescence intensities and their fluctuations well. The variance analysis showed that the depth detection limit in the presence of ambient light increased with the decrease in the source-detector distance, and the optimum distance was in the range of 10 to 15 mm. The depth detection limit was found to be ∼ 30 mm with this optimum distance for the phantom. Conclusions The presented analysis provides a guide for the optimum design of the measurement configuration for detecting fluorescence objects in clinical applications.
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Affiliation(s)
- Goro Nishimura
- Hokkaido University, Research Institute for Electronic Science, Sapporo, Japan
| | - Takahiro Suzuki
- The University of Electro-Communications, Graduate School of Informatics and Engineering, Chofu, Japan
| | - Yukio Yamada
- The University of Electro-Communications, Center for Neuroscience and Biomedical Engineering, Chofu, Japan
| | - Haruki Niwa
- The University of Electro-Communications, Center for Neuroscience and Biomedical Engineering, Chofu, Japan
| | - Takuji Koike
- The University of Electro-Communications, Graduate School of Informatics and Engineering, Chofu, Japan
- The University of Electro-Communications, Center for Neuroscience and Biomedical Engineering, Chofu, Japan
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41
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Ersan M, Kaya B, Özdemir A, Durdurur Çin A, Ergün H. Challenges in flap monitoring with indocyanine green angiography in experimental models. Heliyon 2024; 10:e36034. [PMID: 39262978 PMCID: PMC11388392 DOI: 10.1016/j.heliyon.2024.e36034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 08/08/2024] [Accepted: 08/08/2024] [Indexed: 09/13/2024] Open
Abstract
Introduction Non-invasive angiography with indocyanine green dye facilitates the assessment of flaps. Although ICG angiography has been successfully utilized in clinical settings for human beings, its application in experimental models exhibits certain limitations. This study aimed to address the encountered issues in angiography with different experimental models and introduce a novel modification to the ICG imaging of the McFarlane flap. Materials-methods Rats were randomly divided into three groups: the first group received an epigastric flap (n = 4), the second group received a deep inferior epigastric perforator flap (n = 4), and the third group received a dorsal flap (n = 8). In the first group, sterile silicone background was placed under two flaps. In the second group, no background was used. In the third group, a sterile silicone or aluminum foil was placed under the flaps. Flap perfusions were assessed using fluorescent imaging after flap adaptations, at postoperative 30th minute and 3., 5. and 7. days. Necrosis calculations were performed using all images obtained from the digital camera and the fluorescent imaging. In the third group, the flow velocities were also calculated. All flaps were sent for histopathological examination. Results Even with a silicone background, clear perfusion evaluation and determining the threshold value for predicting necrosis rates were challenging. Moreover, a portion of the flaps without background material survived as grafts. Using an aluminum foil background improved image quality by reducing reflection from interior organs. Conclusion The use of an aluminum foil background is beneficial in non-invasive angiography for assessing flap perfusions accurately and predicting necrosis in experimental animal models.
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Affiliation(s)
- Mert Ersan
- Ankara University Faculty of Medicine, Plastic Reconstructive and Aesthetic Surgery Department, 06110, Turkiye
| | - Burak Kaya
- Ankara University Faculty of Medicine, Plastic Reconstructive and Aesthetic Surgery Department, 06110, Turkiye
| | - Arda Özdemir
- Ankara University Faculty of Medicine, Plastic Reconstructive and Aesthetic Surgery Department, 06110, Turkiye
| | - Aygül Durdurur Çin
- Ankara University Faculty of Medicine, Department of Medical Pharmacology, 06110, Turkiye
| | - Hakan Ergün
- Ankara University Faculty of Medicine, Department of Medical Pharmacology, 06110, Turkiye
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42
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Cabello MC, Chen G, Melville MJ, Osman R, Kumar GD, Domaille DW, Lippert AR. Ex Tenebris Lux: Illuminating Reactive Oxygen and Nitrogen Species with Small Molecule Probes. Chem Rev 2024; 124:9225-9375. [PMID: 39137397 DOI: 10.1021/acs.chemrev.3c00892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2024]
Abstract
Reactive oxygen and nitrogen species are small reactive molecules derived from elements in the air─oxygen and nitrogen. They are produced in biological systems to mediate fundamental aspects of cellular signaling but must be very tightly balanced to prevent indiscriminate damage to biological molecules. Small molecule probes can transmute the specific nature of each reactive oxygen and nitrogen species into an observable luminescent signal (or even an acoustic wave) to offer sensitive and selective imaging in living cells and whole animals. This review focuses specifically on small molecule probes for superoxide, hydrogen peroxide, hypochlorite, nitric oxide, and peroxynitrite that provide a luminescent or photoacoustic signal. Important background information on general photophysical phenomena, common probe designs, mechanisms, and imaging modalities will be provided, and then, probes for each analyte will be thoroughly evaluated. A discussion of the successes of the field will be presented, followed by recommendations for improvement and a future outlook of emerging trends. Our objectives are to provide an informative, useful, and thorough field guide to small molecule probes for reactive oxygen and nitrogen species as well as important context to compare the ecosystem of chemistries and molecular scaffolds that has manifested within the field.
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Affiliation(s)
- Maidileyvis C Cabello
- Department of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United States
| | - Gen Chen
- Department of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United States
| | - Michael J Melville
- Department of Chemistry, Colorado School of Mines, Golden, Colorado 80401, United States
| | - Rokia Osman
- Department of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United States
| | - G Dinesh Kumar
- Department of Chemistry, Colorado School of Mines, Golden, Colorado 80401, United States
| | - Dylan W Domaille
- Department of Chemistry, Colorado School of Mines, Golden, Colorado 80401, United States
| | - Alexander R Lippert
- Department of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United States
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43
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Feng C, Jiang X, Feng L, Sun W, Liu Q, Hao Y, Cui B. Comparison of different tracers in sentinel lymph node detection for endometrial cancer: A systematic review and network meta-analysis. Int J Surg 2024; 111:01279778-990000000-01922. [PMID: 39185991 PMCID: PMC11745743 DOI: 10.1097/js9.0000000000002064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 08/11/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND In the realm of endometrial cancer (EC) therapeutics and prognostic assessments, lymph nodes' status is paramount. The sentinel lymph node (SLN) detection, recognized for its reliability, has been progressively adopted as a standard procedure, posing a compelling alternative to conventional systematic lymphadenectomy. However, there remains a lack of agreement on the most effective choice of tracers for this procedure. OBJECTIVE This investigation was dedicated to a comparative analysis of various tracers to identify the most effective combination that achieves the highest detection rate. This endeavor sought to enhance the efficacy of SLN biopsy in the surgical management of EC. METHODS A systematic review was conducted across multiple databases, including the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Embase, and clinicaltrials.gov, to analyze studies employing different tracers for SLN biopsy during surgery in EC. Using Bayesian network meta-analysis, we compared the total and bilateral detection rates of various tracers. RESULTS After screening 1431 articles, 11 studies including 2699 participants were selected in this network meta-analysis. The combination of radioactive isotopes and indocyanine green (ICG) emerged as the most efficacious method in total and bilateral detection rates, with the Surface Under the Cumulative Ranking Curve (SUCRA) scores of 80.00% and 86.36%, respectively. Additionally, carbon nanoparticles (CNPs) demonstrated superior performance in the detection of para-aortic lymph nodes with an SUCRA score of 97.77%. CONCLUSION Network meta-analysis shows that the application of radioactive isotopes and ICG is the optimal tracer combination for SLN biopsy during surgery in EC.
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Affiliation(s)
| | | | | | | | | | | | - Baoxia Cui
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Shandong Province, People’s Republic of China
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Guo L, Yang M, Dong B, Lewman S, Van Horn A, Jia S. Engineering Central Substitutions in Heptamethine Dyes for Improved Fluorophore Performance. JACS AU 2024; 4:3007-3017. [PMID: 39211623 PMCID: PMC11350720 DOI: 10.1021/jacsau.4c00343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 07/27/2024] [Accepted: 07/29/2024] [Indexed: 09/04/2024]
Abstract
As a major family of red-shifted fluorophores that operate beyond visible light, polymethine dyes are pivotal in light-based biological techniques. However, methods for tuning this kind of fluorophores by structural modification remain restricted to bottom-up synthesis and modification using coupling or nucleophilic substitutions. In this study, we introduce a two-step, late-stage functionalization process for heptamethine dyes. This process enables the substitution of the central chlorine atom in the commonly used 4'-chloro heptamethine scaffold with various aryl groups using aryllithium reagents. This method borrows the building block and designs from the xanthene dye community and offers a mild and convenient way for the diversification of heptamethine fluorophores. Notably, this efficient conversion allows for the synthesis of heptamethine-X, the heptamethine scaffold with two ortho-substituents on the 4'-aryl modification, which brings enhanced stability and reduced aggregation to the fluorophore. We showcase the utility of this method by a facile synthesis of a fluorogenic, membrane-localizing fluorophore that outperforms its commercial counterparts with a significantly higher brightness and contrast. Overall, this method establishes the synthetic similarities between polymethine and xanthene fluorophores and provides a versatile and feasible toolbox for future optimizing heptamethine fluorophores for their biological applications.
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Affiliation(s)
- Lei Guo
- Department
of Civil Engineering, University of Arkansas,
Fayetteville, Fayetteville, Arkansas 72701, United States
| | - Meek Yang
- Department
of Chemistry and Biochemistry, University
of Arkansas, Fayetteville, Fayetteville, Arkansas 72701, United States
| | - Bin Dong
- Department
of Chemistry and Biochemistry, University
of Arkansas, Fayetteville, Fayetteville, Arkansas 72701, United States
| | - Seth Lewman
- Department
of Chemistry and Biochemistry, University
of Arkansas, Fayetteville, Fayetteville, Arkansas 72701, United States
| | - Alex Van Horn
- Department
of Chemistry and Biochemistry, University
of Arkansas, Fayetteville, Fayetteville, Arkansas 72701, United States
| | - Shang Jia
- Department
of Chemistry and Biochemistry, University
of Arkansas, Fayetteville, Fayetteville, Arkansas 72701, United States
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Kumari P, Arora S, Pan Y, Ahmed I, Kumar S, Parshad B. Tailoring Indocyanine Green J-Aggregates for Imaging, Cancer Phototherapy, and Drug Delivery: A Review. ACS APPLIED BIO MATERIALS 2024; 7:5121-5135. [PMID: 39039943 DOI: 10.1021/acsabm.4c00651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/24/2024]
Abstract
Indocyanine green J-aggregates (ICG-Jagg) have emerged as a significant subject of interest in biomedical applications due to their unique optical properties, tunable size, and excellent biocompatibility. This comprehensive review aims to provide an in-depth exploration of ICG-Jagg, with a focus on elucidating the diverse facets of their preparation and the factors that influence the preparation process. Additionally, the review discusses their applications in biomedical diagnostics, such as imaging and contrast agents, as well as their utilization in drug delivery and various phototherapeutic interventions.
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Affiliation(s)
- Pooja Kumari
- Department of Chemistry, Deenbandhu Chhoturam University of Science and Technology, Sonipat 131039, Murthal, India
| | - Smriti Arora
- Institut für Chemie und Biochemie Organische Chemie, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany
| | - Yuanwei Pan
- Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China
| | - Ishtiaq Ahmed
- Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, U.K
| | - Sumit Kumar
- Department of Chemistry, Deenbandhu Chhoturam University of Science and Technology, Sonipat 131039, Murthal, India
| | - Badri Parshad
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, United States
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46
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Alotaibi H, Hatahet T, Al-Jamal WT. Indocyanine green J-aggregate (IJA) theranostics: Challenges and opportunities. Int J Pharm 2024; 661:124456. [PMID: 38986962 DOI: 10.1016/j.ijpharm.2024.124456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 07/06/2024] [Accepted: 07/08/2024] [Indexed: 07/12/2024]
Abstract
Indocyanine green is an FDA-approved fluorescent imaging dye used for determining cardiac output, hepatic function, liver blood flow, and retinal perfusion. It has been investigated preclinically in photoacoustic imaging and photothermal therapy (PTT); however, ICG photodegradation limits its biomedical applications. An aggregated form of ICG, known as J-aggregate (IJA), exhibits superior photoacoustic signals and thermal stability than the monomeric ICG. Nevertheless, IJA still suffers from low stability in the biological milieu, and short in vivo blood circulation. To address these limitations, a range of nanocarriers have been developed to enhance IJA stability and performance. This review focuses on IJA potentials and limitations, besides the recent development of IJA-loaded nanocarriers, particularly for cancer imaging and therapy.
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Affiliation(s)
- Hamoud Alotaibi
- School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom; Department of Pharmaceutics, College of Pharmacy, Northern Border University, Arar 91431, Saudi Arabia
| | - Taher Hatahet
- School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom; China Medical University and Queen's University Joint College, Shenyang, People's Republic of China
| | - Wafa' T Al-Jamal
- School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom.
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Koning S, van Kersen J, Tange FP, Kruiswijk MW, Peul RC, van Schaik J, Schepers A, Vahrmeijer AL, Hamming JF, van den Hoven P, van der Vorst JR. The impact of diabetes mellitus on foot perfusion measured by ICG NIR fluorescence imaging. Diabetes Res Clin Pract 2024; 214:111772. [PMID: 38972600 DOI: 10.1016/j.diabres.2024.111772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 07/02/2024] [Accepted: 07/05/2024] [Indexed: 07/09/2024]
Abstract
INTRODUCTION Diabetes Mellitus (DM) is a common chronic disease, affecting 435 million people globally. Impaired vasculature in DM patients leads to complications like lower extremity arterial disease (LEAD) and foot ulcers, often resulting in amputations. DM causes additional peripheral neuropathy leading to multifactorial wound problems. Current diagnostics often deem unreliable, but Near-Infrared Fluorescence with Indocyanine Green (ICG NIR) can be used to assess the foot perfusion. Therefore, this study explores DM's impact on foot perfusion using ICG NIR. METHODS Baseline ICG NIR fluorescence imaging was performed in LEAD patients with and without DM. Ten perfusion parameters were extracted and analyzed to assess differences in perfusion patterns. RESULTS Among 109 patients (122 limbs) of the included patients, 32.8 % had DM. Six of ten perfusion parameters, mainly inflow-related, differed significantly between DM and non-DM patients (p-values 0.007-0.039). Fontaine stage 4 DM patients had the highest in- and outflow values, with seven parameters significantly higher (p-values 0.004-0.035). CONCLUSION DM is associated with increased in- and outflow parameters. Patients with- and without DM should not be compared directly due to different vascular pathophysiology and multifactorial wound problems in DM patients. Quantified ICG NIR fluorescence imaging offers additional insight into the effect of DM on foot perfusion.
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Affiliation(s)
- Stefan Koning
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Just van Kersen
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Floris P Tange
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Mo W Kruiswijk
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Roderick C Peul
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Jan van Schaik
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Abbey Schepers
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Alexander L Vahrmeijer
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Jaap F Hamming
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Pim van den Hoven
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Joost R van der Vorst
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
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Zajac J, Liu A, Hassan S, Gibson A. Mechanisms of delayed indocyanine green fluorescence and applications to clinical disease processes. Surgery 2024; 176:386-395. [PMID: 38749795 PMCID: PMC11246809 DOI: 10.1016/j.surg.2024.03.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 03/15/2024] [Accepted: 03/28/2024] [Indexed: 07/16/2024]
Abstract
BACKGROUND Delayed indocyanine green fluorescence imaging is under investigation in various clinical disease processes. Understanding the mechanisms of indocyanine green accumulation and retention is essential to correctly interpreting and analyzing imaging data. The purpose of this scoping review was to synthesize what is known about the mechanism of indocyanine green retention at the cellular level to better understand the clinical nuances of delayed indocyanine green imaging and identify critical gaps in our knowledge to guide future studies. METHODS We performed a scoping review of 7,087 citations after performing database searches of PubMed, Scopus, the Cochrane Library, and the Web of Science Core Collection electronic databases. Studies were eligible for inclusion if they were peer-reviewed original research discussing the mechanism of indocyanine green retention in the results section in disease processes involving inflammation and/or necrosis, including cancer, and were available in English. Data were extracted using Covidence software. RESULTS Eighty-nine studies were included in the final analysis. Several features of indocyanine green retention were identified. CONCLUSION We identified several mechanistic features involved in indocyanine green accumulation in diseased tissue that overall had distinct mechanisms of indocyanine green retention in tumors, nontumor inflammation, and necrosis. Our study also reveals new insights on how inflammatory infiltrate influences indocyanine green fluorescence imaging. These findings are noteworthy because they add to our understanding of how fluorescence-guided surgery may be optimized based on the pathology of interest via specific indocyanine green dosing and timing of image acquisition.
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Affiliation(s)
- Jocelyn Zajac
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Aiping Liu
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Sameeha Hassan
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Angela Gibson
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI.
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Boland PA, Hardy NP, Moynihan A, McEntee PD, Loo C, Fenlon H, Cahill RA. Intraoperative near infrared functional imaging of rectal cancer using artificial intelligence methods - now and near future state of the art. Eur J Nucl Med Mol Imaging 2024; 51:3135-3148. [PMID: 38858280 PMCID: PMC11300525 DOI: 10.1007/s00259-024-06731-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 04/15/2024] [Indexed: 06/12/2024]
Abstract
Colorectal cancer remains a major cause of cancer death and morbidity worldwide. Surgery is a major treatment modality for primary and, increasingly, secondary curative therapy. However, with more patients being diagnosed with early stage and premalignant disease manifesting as large polyps, greater accuracy in diagnostic and therapeutic precision is needed right from the time of first endoscopic encounter. Rapid advancements in the field of artificial intelligence (AI), coupled with widespread availability of near infrared imaging (currently based around indocyanine green (ICG)) can enable colonoscopic tissue classification and prognostic stratification for significant polyps, in a similar manner to contemporary dynamic radiological perfusion imaging but with the advantage of being able to do so directly within interventional procedural time frames. It can provide an explainable method for immediate digital biopsies that could guide or even replace traditional forceps biopsies and provide guidance re margins (both areas where current practice is only approximately 80% accurate prior to definitive excision). Here, we discuss the concept and practice of AI enhanced ICG perfusion analysis for rectal cancer surgery while highlighting recent and essential near-future advancements. These include breakthrough developments in computer vision and time series analysis that allow for real-time quantification and classification of fluorescent perfusion signals of rectal cancer tissue intraoperatively that accurately distinguish between normal, benign, and malignant tissues in situ endoscopically, which are now undergoing international prospective validation (the Horizon Europe CLASSICA study). Next stage advancements may include detailed digital characterisation of small rectal malignancy based on intraoperative assessment of specific intratumoral fluorescent signal pattern. This could include T staging and intratumoral molecular process profiling (e.g. regarding angiogenesis, differentiation, inflammatory component, and tumour to stroma ratio) with the potential to accurately predict the microscopic local response to nonsurgical treatment enabling personalised therapy via decision support tools. Such advancements are also applicable to the next generation fluorophores and imaging agents currently emerging from clinical trials. In addition, by providing an understandable, applicable method for detailed tissue characterisation visually, such technology paves the way for acceptance of other AI methodology during surgery including, potentially, deep learning methods based on whole screen/video detailing.
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Affiliation(s)
- Patrick A Boland
- UCD Centre for Precision Surgery, School of Medicine, University College Dublin, 47 Eccles Street, Dublin 7, Dublin, Ireland
- Department of Colorectal Surgery, Mater Misericordiae University Hospital, Dublin, Ireland
| | - N P Hardy
- UCD Centre for Precision Surgery, School of Medicine, University College Dublin, 47 Eccles Street, Dublin 7, Dublin, Ireland
- Department of Colorectal Surgery, Mater Misericordiae University Hospital, Dublin, Ireland
| | - A Moynihan
- UCD Centre for Precision Surgery, School of Medicine, University College Dublin, 47 Eccles Street, Dublin 7, Dublin, Ireland
- Department of Colorectal Surgery, Mater Misericordiae University Hospital, Dublin, Ireland
| | - P D McEntee
- UCD Centre for Precision Surgery, School of Medicine, University College Dublin, 47 Eccles Street, Dublin 7, Dublin, Ireland
- Department of Colorectal Surgery, Mater Misericordiae University Hospital, Dublin, Ireland
| | - C Loo
- UCD Centre for Precision Surgery, School of Medicine, University College Dublin, 47 Eccles Street, Dublin 7, Dublin, Ireland
| | - H Fenlon
- Department of Radiology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - R A Cahill
- UCD Centre for Precision Surgery, School of Medicine, University College Dublin, 47 Eccles Street, Dublin 7, Dublin, Ireland.
- Department of Colorectal Surgery, Mater Misericordiae University Hospital, Dublin, Ireland.
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Wen Y, Wang J, Zheng W, Zhu J, Song X, Chen T, Zhang M, Huang Z, Li J. A supramolecular colloidal system based on folate-conjugated β-cyclodextrin polymer and indocyanine green for enhanced tumor-targeted cell imaging in 2D culture and 3D tumor spheroids. J Colloid Interface Sci 2024; 667:259-268. [PMID: 38636227 DOI: 10.1016/j.jcis.2024.04.072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 04/04/2024] [Accepted: 04/10/2024] [Indexed: 04/20/2024]
Abstract
Indocyanine green (ICG) is an FDA-approved medical diagnostic agent that is widely used as a near-infrared (NIR) fluorescent imaging molecular probe. However, ICG tends to aggregate to form dimers or H-aggregates in water and lacks physical and optical stability, which greatly decreases its absorbance and fluorescence intensity in various applications. Additionally, ICG has no tissue- or tumor-targeting properties, and its structure is not easy to modify, which has further limited its application in cancer diagnosis. In this study, we addressed these challenges by developing a supramolecular colloidal carrier system that targets tumor cells. To this end, we synthesized a water-soluble β-cyclodextrin (β-CD) polymer conjugated with folate (FA), denoted PCD-FA, which is capable of forming inclusion complexes with ICG in water through host-guest interactions between the β-CD moieties and ICG molecules. The inclusion complexes formed by PCD-FA and ICG, called ICG@PCD-FA, dispersed stably in solution as colloidal nanoparticles, greatly improving the physical and optical properties of ICG by preventing ICG dimer formation, where ICG appeared as monomers and even J-aggregates. This resulted in stronger and more stable absorption at a longer wavelength of 900 nm, which may allow for deeper tissue penetration and imaging with reduced interference from biological tissues' autofluorescence. Moreover, ICG@PCD-FA showed a targeting effect on folate receptor-positive (FR+) tumor cells, which specifically highlighted FR+ cells via NIR endoscopic imaging. Notably, ICG@PCD-FA further improved permeation and accumulation in FR+ 3D tumor spheroids. Therefore, this ICG@PCD-FA supramolecular colloidal system may have a great potential for use in tumor NIR imaging and diagnostic applications.
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Affiliation(s)
- Yuting Wen
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore; National University of Singapore (Suzhou) Research Institute, Suzhou, Jiangsu 215000, China; National University of Singapore (Chongqing) Research Institute, Yubei District, Chongqing 401120, China
| | - Jianfeng Wang
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore
| | - Wei Zheng
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore
| | - Jingling Zhu
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore; NUS Environmental Research Institute (NERI), National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore
| | - Xia Song
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore
| | - Taili Chen
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore
| | - Miao Zhang
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore
| | - Zhiwei Huang
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore; NUS Environmental Research Institute (NERI), National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore.
| | - Jun Li
- Department of Biomedical Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore; National University of Singapore (Suzhou) Research Institute, Suzhou, Jiangsu 215000, China; National University of Singapore (Chongqing) Research Institute, Yubei District, Chongqing 401120, China; NUS Environmental Research Institute (NERI), National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore.
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