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Murugan D, Thirumalaiswamy HV, Murugesan V, Venkatesan J, Balachandran U, Lakshminarayanan K, Satpati D, Nikolić S, Rangasamy L. Unlocking the power of affibody conjugated radioactive metallopharmaceuticals for targeted cancer diagnosis and therapy. Pharmacol Ther 2025:108863. [PMID: 40294752 DOI: 10.1016/j.pharmthera.2025.108863] [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: 10/28/2024] [Revised: 03/02/2025] [Accepted: 04/20/2025] [Indexed: 04/30/2025]
Abstract
Cancer is the second-largest death-causing disease after cardiovascular diseases. Effective research on cancer diagnosis and subsequent elimination plays a vital role in reducing the cancer-related death toll. Radiotherapy is one of the best strategies that could kill masses of solid tumour tissues; however, the efficacy is limited due to the bystander effect. This issue could be solved by the emergence of targeted delivery of radiometallic complexes, enabling clinicians to monitor the tumour regions and effectively destroy the tumour. Affibody® molecules are a class of synthetic peptides known as antibody mimics having the binding sites of an antibody. The specificity of affibodies is found to be greater than that of antibodies due to their small size. This review intends to highlight the recent developments in the field of affibody-targeted radiometallopharmaceuticals. These approaches could be essential for early cancer detection, tumour staging, and monitoring the response to therapy and could produce better therapeutic outcomes. In an attempt to provide ideas and inspiration for the researchers to design affibody-conjugated radiopharmaceuticals that are clinically applicable, we have provided an in-depth exploration of the various types of affibody-conjugated radiopharmaceuticals that are currently in clinical trials and various other pre-clinically tested conjugates in this article. Only a few review reports on affibody-conjugated radiometallopharmaceuticals, typically focusing on a specific molecular target or radionuclides reported. In this review, we provide a comprehensive overview of most radiometals, such as 111In, 68Ga, 64Cu, 55Co, 57Co, 44Sc, 99mTc, 89Zr, 90Y, 211At, 188Re, and 177Lu, choice of chelators, and potential cancer-associated molecular targets such HER2, EGFR or HER1, HER3, IGF-1R, PDGFRβ, VEGFR2, PD-L1, CAIX, PD-L1, neonatal Fc receptor (FcRn) and B7-H3. This approach highlights the advancements made over the past twenty years in affibody conjugates for radio imaging and therapy in oncology.
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Affiliation(s)
- Dhanashree Murugan
- Drug Discovery Unit (DDU), Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; School of Biosciences & Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Harashkumar Vasanthakumari Thirumalaiswamy
- Drug Discovery Unit (DDU), Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Vasanth Murugesan
- Drug Discovery Unit (DDU), Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Janarthanan Venkatesan
- Drug Discovery Unit (DDU), Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Unnikrishnan Balachandran
- Drug Discovery Unit (DDU), Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Kalaiarasu Lakshminarayanan
- Drug Discovery Unit (DDU), Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; School of Advanced Sciences (SAS), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Drishty Satpati
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre (BARC), Mumbai, Maharashtra 400085, India; Homi Bhabha National Institute, Mumbai 400094, India
| | - Stefan Nikolić
- Innovative Centre of the Faculty of Chemistry Belgrade, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia
| | - Loganathan Rangasamy
- Drug Discovery Unit (DDU), Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India.
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Fathi M, Taher HJ, Al-Rubiae SJ, Yaghoobpoor S, Bahrami A, Eshraghi R, Sadri H, Asadi Anar M, Gholamrezanezhad A. Role of molecular imaging in prognosis, diagnosis, and treatment of gastrointestinal cancers: An update on new therapeutic methods. World J Methodol 2024; 14:93461. [PMID: 39712556 PMCID: PMC11287540 DOI: 10.5662/wjm.v14.i4.93461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 05/31/2024] [Accepted: 07/15/2024] [Indexed: 07/26/2024] Open
Abstract
One of the leading causes of cancer-related death is gastrointestinal cancer, which has a significant morbidity and mortality rate. Although preoperative risk assessment is essential for directing patient care, its biological behavior cannot be accurately predicted by conventional imaging investigations. Potential pathophysiological information in anatomical imaging that cannot be visually identified can now be converted into high-dimensional quantitative image features thanks to the developing discipline of molecular imaging. In order to enable molecular tissue profile in vivo, molecular imaging has most recently been utilized to phenotype the expression of single receptors and targets of biological therapy. It is expected that molecular imaging will become increasingly important in the near future, driven by the expanding range of biological therapies for cancer. With this live molecular fingerprinting, molecular imaging can be utilized to drive expression-tailored customized therapy. The technical aspects of molecular imaging are first briefly discussed in this review, followed by an examination of the most recent research on the diagnosis, prognosis, and potential future clinical methods of molecular imaging for GI tract malignancies.
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Affiliation(s)
- Mobina Fathi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran
| | | | | | - Shirin Yaghoobpoor
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran
| | - Ashkan Bahrami
- Faculty of Medicine, Kashan University of Medical Sciences, Kashan 1617768911, Iran
| | - Reza Eshraghi
- Faculty of Medicine, Kashan University of Medical Sciences, Kashan 1617768911, Iran
| | - Hossein Sadri
- Faculty of Medicine, Kashan University of Medical Sciences, Kashan 1617768911, Iran
| | - Mahsa Asadi Anar
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran
| | - Ali Gholamrezanezhad
- Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States
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Al-Ibraheem A, Abdlkadir A, Herrmann K, Bomanji J, Jadvar H, Shi H, Mansour A, Paez D, Chiti A, Scott AM. Diagnostic Accuracy of [ 18F]FDG PET/MRI in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Metaanalysis. J Nucl Med 2024; 65:1533-1539. [PMID: 39266291 DOI: 10.2967/jnumed.124.268049] [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: 05/06/2024] [Accepted: 07/04/2024] [Indexed: 09/14/2024] Open
Abstract
This study evaluates the diagnostic utility of PET/MRI for primary, locoregional, and nodal head and neck squamous cell carcinoma (HNSCC) through systematic review and metaanalysis. Methods: A systematic search was conducted using PubMed and Scopus to identify studies on the diagnostic accuracy of PET/MRI for HNSCC. The search included specific terms and excluded nonhybrid PET/MRI studies, and those with a sample size of fewer than 10 patients were excluded. Results: In total, 15 studies encompassing 638 patients were found addressing the diagnostic test accuracy for PET/MRI within the chosen subject domain. Squamous cell carcinoma of the nasopharynx was the most observed HNSCC subtype (n = 198). The metaanalysis included 12 studies, with pooled sensitivity and specificity values of 93% and 95% per patient for primary disease evaluation, 93% and 96% for locoregional evaluation, and 89% and 98% per lesion for nodal disease detection, respectively. An examination of a subset of studies comparing PET/MRI against PET/CT or MRI alone for evaluating nodal and locoregional HNSCC found that PET/MRI may offer slightly higher accuracy than other modalities. However, this difference was not statistically significant. Conclusion: PET/MRI has excellent potential for identifying primary, locoregional, and nodal HNSCC.
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Affiliation(s)
- Akram Al-Ibraheem
- Department of Nuclear Medicine, King Hussein Cancer Center, Amman, Jordan;
- School of Medicine, University of Jordan, Amman, Jordan
| | - Ahmed Abdlkadir
- Department of Nuclear Medicine, King Hussein Cancer Center, Amman, Jordan
| | - Ken Herrmann
- Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
- German Cancer Consortium, Partner Site University Hospital Essen, Essen, Germany
| | - Jamshed Bomanji
- Institute of Nuclear Medicine, University College London, London, United Kingdom
| | - Hossein Jadvar
- Division of Nuclear Medicine and Molecular Imaging, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Hongcheng Shi
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Asem Mansour
- Department of Radiology, King Hussein Cancer Center, Amman, Jordan
| | - Diana Paez
- Nuclear Medicine and Diagnostic Imaging Section, International Atomic Energy Agency, Vienna, Austria
| | - Arturo Chiti
- Department of Nuclear Medicine, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Andrew M Scott
- Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia; and
- Olivia Newton-John Cancer Research Institute and La Trobe University, Heidelberg, Victoria, Australia
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Ehrhorn EG, Lovell P, Svechkarev D, Romanova S, Mohs AM. Optimizing the performance of silica nanoparticles functionalized with a near-infrared fluorescent dye for bioimaging applications. NANOTECHNOLOGY 2024; 35:10.1088/1361-6528/ad3fc5. [PMID: 38631329 PMCID: PMC11216106 DOI: 10.1088/1361-6528/ad3fc5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 04/17/2024] [Indexed: 04/19/2024]
Abstract
Modified fluorescent nanoparticles continue to emerge as promising candidates for drug delivery, bioimaging, and labeling tools for various biomedical applications. The ability of nanomaterials to fluorescently label cells allow for the enhanced detection and understanding of diseases. Silica nanoparticles have a variety of unique properties that can be harnessed for many different applications, causing their increased popularity. In combination with an organic dye, fluorescent nanoparticles demonstrate a vast range of advantageous properties including long photostability, surface modification, and signal amplification, thus allowing ease of manipulation to best suit bioimaging purposes. In this study, the Stöber method with tetraethyl orthosilicate (TEOS) and a fluorescent dye sulfo-Cy5-amine was used to synthesize fluorescent silica nanoparticles. The fluorescence spectra, zeta potential, quantum yield, cytotoxicity, and photostability were evaluated. The increased intracellular uptake and photostability of the dye-silica nanoparticles show their potential for bioimaging.
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Affiliation(s)
- Evie G. Ehrhorn
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, 68198, United States
| | - Paul Lovell
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, 68198, United States
| | - Denis Svechkarev
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States
- Department of Chemistry, University of Nebraska at Omaha, Omaha, Nebraska 68182, United States
| | - Svetlana Romanova
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States
| | - Aaron M. Mohs
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, 68198, United States
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, 68198, United States
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Ramesh A, Deshpande N, Malik V, Nguyen A, Malhotra M, Debnath M, Brouillard A, Kulkarni A. Activatable Nanoreporters for Real-Time Tracking of Macrophage Phenotypic States Associated with Disease Progression. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023; 19:e2300978. [PMID: 37317008 DOI: 10.1002/smll.202300978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 06/05/2023] [Indexed: 06/16/2023]
Abstract
Diagnosis of inflammatory diseases is characterized by identifying symptoms, biomarkers, and imaging. However, conventional techniques lack the sensitivities and specificities to detect disease early. Here, it is demonstrated that the detection of macrophage phenotypes, from inflammatory M1 to alternatively activated M2 macrophages, corresponding to the disease state can be used to predict the prognosis of various diseases. Activatable nanoreporters that can longitudinally detect the presence of the enzyme Arginase 1, a hallmark of M2 macrophages, and nitric oxide, a hallmark of M1 macrophages are engineered, in real-time. Specifically, an M2 nanoreporter enables the early imaging of the progression of breast cancer as predicted by selectively detecting M2 macrophages in tumors. The M1 nanoreporter enables real-time imaging of the subcutaneous inflammatory response that rises from a local lipopolysccharide (LPS) administration. Finally, the M1-M2 dual nanoreporter is evaluated in a muscle injury model, where an initial inflammatory response is monitored by imaging M1 macrophages at the site of inflammation, followed by a resolution phase monitored by the imaging of infiltrated M2 macrophages involved in matrix regeneration and wound healing. It is anticipated that this set of macrophage nanoreporters may be utilized for early diagnosis and longitudinal monitoring of inflammatory responses in various disease models.
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Affiliation(s)
- Anujan Ramesh
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA, 01003, USA
| | - Nilesh Deshpande
- Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA, 01003, USA
| | - Vaishali Malik
- Department of Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA, 01003, USA
| | - Anh Nguyen
- Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA, 01003, USA
| | - Mehak Malhotra
- Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA, 01003, USA
| | - Maharshi Debnath
- Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA, 01003, USA
| | - Anthony Brouillard
- Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA, 01003, USA
| | - Ashish Kulkarni
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA, 01003, USA
- Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA, 01003, USA
- Department of Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA, 01003, USA
- Center for Bioactive Delivery, Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA, 01003, USA
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Yavuz M, Ütkür M, Kehribar EŞ, Yağız E, Sarıtaş EÜ, Şeker UÖŞ. Engineered Bacteria with Genetic Circuits Accumulating Nanomagnets as MRI Contrast Agents. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2200537. [PMID: 35567331 DOI: 10.1002/smll.202200537] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 04/23/2022] [Indexed: 06/15/2023]
Abstract
The demand for highly efficient cancer diagnostic tools increases alongside the high cancer incidence nowadays. Moreover, there is an imperative need for novel cancer treatment therapies that lack the side effects of conventional treatment options. Developments in this aspect employ magnetic nanoparticles (MNPs) for biomedical applications due to their stability, biocompatibility, and magnetic properties. Certain organisms, including many bacteria, can synthesize magnetic nanocrystals, which help their spatial orientation and survival by sensing the earth's geomagnetic field. This work aims to convert Escherichia coli to accumulate magnetite, which can further be coupled with drug delivery modules. The authors design magnetite accumulating bacterial machines using genetic circuitries hiring Mms6 with iron-binding activity and essential in magnetite crystal formation. The work demonstrates that the combinatorial effect of Mms6 with ferroxidase, iron transporter protein, and material binding peptide enhances the paramagnetic behavior of the cells in magnetic resonance imaging (MRI) measurements. Cellular machines are also engineered to display Mms6 peptide on the cell surface via an autotransporter protein that shows augmented MRI performance. The findings are promising for endowing a probiotic bacterium, able to accumulate magnetite intracellularly or extracellularly, serving as a theranostics agent for cancer diagnostics via MRI scanning and hyperthermia treatment.
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Affiliation(s)
- Merve Yavuz
- UNAM- Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center, Bilkent University, Ankara, 06800, Turkey
| | - Mustafa Ütkür
- Department of Electrical and Electronics Engineering, Bilkent University, Ankara, 06800, Turkey
- National Magnetic Resonance Research Center (UMRAM), Bilkent University, Ankara, 06800, Turkey
| | - Ebru Şahin Kehribar
- UNAM- Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center, Bilkent University, Ankara, 06800, Turkey
| | - Ecrin Yağız
- Department of Electrical and Electronics Engineering, Bilkent University, Ankara, 06800, Turkey
- National Magnetic Resonance Research Center (UMRAM), Bilkent University, Ankara, 06800, Turkey
| | - Emine Ülkü Sarıtaş
- Department of Electrical and Electronics Engineering, Bilkent University, Ankara, 06800, Turkey
- National Magnetic Resonance Research Center (UMRAM), Bilkent University, Ankara, 06800, Turkey
- Neuroscience Graduate Program, Bilkent University, Ankara, 06800, Turkey
| | - Urartu Özgür Şafak Şeker
- UNAM- Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center, Bilkent University, Ankara, 06800, Turkey
- Neuroscience Graduate Program, Bilkent University, Ankara, 06800, Turkey
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Ayuso JM, Virumbrales-Muñoz M, Lang JM, Beebe DJ. A role for microfluidic systems in precision medicine. Nat Commun 2022; 13:3086. [PMID: 35654785 PMCID: PMC9163169 DOI: 10.1038/s41467-022-30384-7] [Citation(s) in RCA: 92] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 04/28/2022] [Indexed: 02/08/2023] Open
Abstract
Precision oncology continues to challenge the "one-size-fits-all" dogma. Under the precision oncology banner, cancer patients are screened for molecular tumor alterations that predict treatment response, ideally leading to optimal treatments. Functional assays that directly evaluate treatment efficacy on the patient's cells offer an alternative and complementary tool to improve the accuracy of precision oncology. Unfortunately, traditional Petri dish-based assays overlook much tumor complexity, limiting their potential as predictive functional biomarkers. Here, we review past applications of microfluidic systems for precision medicine and discuss the present and potential future role of functional microfluidic assays as treatment predictors.
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Affiliation(s)
- Jose M Ayuso
- Department of Dermatology, University of Wisconsin, Madison, WI, USA
- Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA
- The University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI, USA
| | - María Virumbrales-Muñoz
- Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA
- The University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI, USA
| | - Joshua M Lang
- The University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI, USA
- Department of Medicine, University of Wisconsin, Madison, WI, USA
| | - David J Beebe
- Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA.
- The University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI, USA.
- Department of Pathology & Laboratory Medicine, University of Wisconsin, Madison, WI, USA.
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8
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Böhmer VI, Szymanski W, Feringa BL, Elsinga PH. Multivalent Probes in Molecular Imaging: Reality or Future? Trends Mol Med 2021; 27:379-393. [PMID: 33436332 DOI: 10.1016/j.molmed.2020.12.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 11/17/2020] [Accepted: 12/08/2020] [Indexed: 01/25/2023]
Abstract
The rapidly developing field of molecular medical imaging focuses on specific visualization of (patho)physiological processes through the application of imaging agents (IAs) in multiple clinical modalities. Although our understanding of the principles underlying efficient IAs design has increased tremendously, many IAs still show poor in vivo imaging performance because of low binding affinity and/or specificity. These limitations can be addressed by taking advantage of multivalency, in which multiple copies of a ligand are employed to strengthen the interaction. We critically address specific challenges associated with the application of multivalent compounds in molecular imaging, and we give directions for a stepwise approach to the design of multivalent imaging probes to improve their target binding and pharmacokinetics (PK) for improved diagnostic potential.
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Affiliation(s)
- Verena I Böhmer
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, Hanzeplein 1, 9713, GZ, Groningen, The Netherlands; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747, AF, Groningen, The Netherlands
| | - Wiktor Szymanski
- Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747, AF, Groningen, The Netherlands; Department of Radiology, Medical Imaging Center, University Medical Center Groningen, Hanzeplein 1, 9713, GZ, Groningen, The Netherlands
| | - Ben L Feringa
- Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747, AF, Groningen, The Netherlands
| | - Philip H Elsinga
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, Hanzeplein 1, 9713, GZ, Groningen, The Netherlands.
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10
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Schuerle S, Furubayashi M, Soleimany AP, Gwisai T, Huang W, Voigt C, Bhatia SN. Genetic Encoding of Targeted Magnetic Resonance Imaging Contrast Agents for Tumor Imaging. ACS Synth Biol 2020; 9:392-401. [PMID: 31922737 DOI: 10.1021/acssynbio.9b00416] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Tumor-selective contrast agents have the potential to aid in the diagnosis and treatment of cancer using noninvasive imaging modalities such as magnetic resonance imaging (MRI). Such contrast agents can consist of magnetic nanoparticles incorporating functionalities that respond to cues specific to tumor environments. Genetically engineering magnetotactic bacteria to display peptides has been investigated as a means to produce contrast agents that combine the robust image contrast effects of magnetosomes with the transgenic-targeting peptides displayed on their surface. This work reports the first use of magnetic nanoparticles that display genetically encoded pH low insertion peptide (pHLIP), a long peptide intended to enhance MRI contrast by targeting the extracellular acidity associated with the tumors. To demonstrate the modularity of this versatile platform to incorporate diverse targeting ligands by genetic engineering, we also incorporated the cyclic αv integrin-binding peptide iRGD into separate magnetosomes. Specifically, we investigate their potential for enhanced binding and tumor imaging both in vitro and in vivo. Our experiments indicate that these tailored magnetosomes retain their magnetic properties, making them well suited as T2 contrast agents, while exhibiting an increased binding compared to the binding in wild-type magnetosomes.
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Affiliation(s)
- Simone Schuerle
- Institute for Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, CH-8092 Zurich, Switzerland
| | - Maiko Furubayashi
- Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
- Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Sapporo 062-8517, Japan
| | - Ava P. Soleimany
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
- Harvard Graduate Program in Biophysics, Harvard University, Boston, Massachusetts 02115, United States
- Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
| | - Tinotenda Gwisai
- Institute for Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, CH-8092 Zurich, Switzerland
| | - Wei Huang
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
| | - Christopher Voigt
- Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
| | - Sangeeta N. Bhatia
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
- Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
- Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
- Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
- Marble Center for Cancer Nanomedicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
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11
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Gulin-Sarfraz T, Pryazhnikov E, Zhang J, Khiroug L, Rosenholm J. Chemical and photonic interactions in vitro and in vivo between fluorescent tracer and nanoparticle-based scavenger for enhanced molecular imaging. Mater Today Bio 2019; 2:100010. [PMID: 32159145 PMCID: PMC7061632 DOI: 10.1016/j.mtbio.2019.100010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 06/05/2019] [Indexed: 11/20/2022] Open
Abstract
We hereby present a concept of scavenging excess imaging agent prior to a diagnostic imaging session, consequently allowing for enhanced contrast of signals originating from the tissue area of interest to the signals originating from systemic imaging agent residues. In our study, a prospective silica core-shell nanoparticle-based scavenger was designed and explored for its feasibility to scavenge a specific imaging agent (tracer) in the bloodstream. The developed tracer-scavenger system was first investigated under in vitro conditions to ensure proper binding between tracer and scavenger is taking place, as confirmed by Förster/fluorescence resonance energy transfer studies. In vivo, two-photon imaging was utilized to directly study the interaction of the scavenger particles and the tracer molecules in the vasculature of mice. To our knowledge, a methodological solution for in vivo differentiation between signals, originating from tissue and blood, has not been presented elsewhere.
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Affiliation(s)
- T. Gulin-Sarfraz
- Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland
- Department of Pharmacy, University of Oslo, Oslo, Norway
| | | | - J. Zhang
- College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - L. Khiroug
- Neurotar LtD, Viikinkaari 4, 00790, Helsinki, Finland
| | - J.M. Rosenholm
- Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland
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12
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Kim J, Do EJ, Moinova H, Bae SM, Kang JY, Hong SM, Fink SP, Joo J, Suh YA, Jang SJ, Hwang SW, Park SH, Yang DH, Ye BD, Byeon JS, Choe J, Yang SK, Markowitz SD, Kim SY, Myung SJ. Molecular Imaging of Colorectal Tumors by Targeting Colon Cancer Secreted Protein-2 (CCSP-2). Neoplasia 2017; 19:805-816. [PMID: 28886423 PMCID: PMC5587890 DOI: 10.1016/j.neo.2017.07.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 07/17/2017] [Accepted: 07/24/2017] [Indexed: 12/31/2022] Open
Abstract
A versatile biomarker for detecting colonic adenoma and colon cancer has yet to be developed. Colon cancer secreted protein-2 (CCSP-2) is a protein specifically expressed and secreted in colon adenomas and cancers. We developed a fluorescent imaging method based on CCSP-2 targeting for a more sensitive and specific detection of colorectal tumors. CCSP-2 expression was evaluated in human colon adenoma and colorectal specimens. Anti–CCSP-2 antibody was labeled with a near-infrared fluorescent dye, FPR-675, and molecular imaging of surgical human colorectal tumors was performed. Immunohistochemistry identified CCSP-2 expression in 87.0% of colorectal cancer specimens and 89.5% of colon adenoma specimens. Fluorescence imaging of surgical human colon specimens after spraying treatment with the probe permitted a clear distinction of cancer from paired normal colon tissue (target-to-background ratio, 4.09 ± 0.42; P < .001). CCSP-2 targeting imaging was also evaluated in patient-derived colon cancer xenograft mouse and liver metastasis murine models. CCSP-2–positive colon cancer xenografts and liver metastases were visualized by near-infrared fluorescence imaging after intravenous injection of the probe, which showed significantly higher fluorescence. Our results show that CCSP-2 is a promising marker for colorectal tumor detection in clinical settings and that a CCSP-2–targeting molecular imaging strategy might improve the diagnosis of colorectal tumors in metastatic or recurrent cancers and aid in early colonoscopic detection of premalignant lesions.
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Affiliation(s)
- Jaeil Kim
- Health Screening & Promotion Center, Asan Medical Center, Seoul, Republic of Korea
| | - Eun-Ju Do
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea
| | - Helen Moinova
- Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Sang Mun Bae
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea
| | - Ja Young Kang
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Stephen P Fink
- Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Jinmyoung Joo
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea; Department of Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Ah Suh
- Institute for Innovative Cancer Research, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea
| | - Se Jin Jang
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung Wook Hwang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jaewon Choe
- Health Screening & Promotion Center, Asan Medical Center, Seoul, Republic of Korea; Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sanford D Markowitz
- Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
| | - Sang-Yeob Kim
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea; Department of Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Seung-Jae Myung
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea; Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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13
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Luby BM, Charron DM, MacLaughlin CM, Zheng G. Activatable fluorescence: From small molecule to nanoparticle. Adv Drug Deliv Rev 2017; 113:97-121. [PMID: 27593264 DOI: 10.1016/j.addr.2016.08.010] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 08/15/2016] [Accepted: 08/27/2016] [Indexed: 12/23/2022]
Abstract
Molecular imaging has emerged as an indispensable technology in the development and application of drug delivery systems. Targeted imaging agents report the presence of biomolecules, including therapeutic targets and disease biomarkers, while the biological behaviour of labelled delivery systems can be non-invasively assessed in real time. As an imaging modality, fluorescence offers additional signal specificity and dynamic information due to the inherent responsivity of fluorescence agents to interactions with other optical species and with their environment. Harnessing this responsivity is the basis of activatable fluorescence imaging, where interactions between an engineered fluorescence agent and its biological target induce a fluorogenic response. Small molecule activatable agents are frequently derivatives of common fluorophores designed to chemically react with their target. Macromolecular scale agents are useful for imaging proteins and nucleic acids, although their biological delivery can be difficult. Nanoscale activatable agents combine the responsivity of fluorophores with the unique optical and physical properties of nanomaterials. The molecular imaging application and overall complexity of biological target dictate the most advantageous fluorescence agent size scale and activation strategy.
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Affiliation(s)
- Benjamin M Luby
- Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, ON, Canada
| | - Danielle M Charron
- Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, ON, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada
| | - Christina M MacLaughlin
- Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, ON, Canada
| | - Gang Zheng
- Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, ON, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
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14
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Valluru KS, Willmann JK. Clinical photoacoustic imaging of cancer. Ultrasonography 2016; 35:267-80. [PMID: 27669961 PMCID: PMC5040138 DOI: 10.14366/usg.16035] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Revised: 08/30/2016] [Accepted: 08/30/2016] [Indexed: 12/12/2022] Open
Abstract
Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.
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Affiliation(s)
- Keerthi S. Valluru
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA
| | - Juergen K. Willmann
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA
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15
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Anani T, Panizzi P, David AE. Nanoparticle-based probes to enable noninvasive imaging of proteolytic activity for cancer diagnosis. Nanomedicine (Lond) 2016; 11:2007-22. [PMID: 27465386 PMCID: PMC5941711 DOI: 10.2217/nnm-2016-0027] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Accepted: 05/23/2016] [Indexed: 12/20/2022] Open
Abstract
Proteases play a key role in tumor biology, with high expression levels often correlating with poor prognosis for cancer patients - making them excellent disease markers for tumor diagnosis. Despite their significance, quantifying proteolytic activity in vivo remains a challenge. Nanoparticles, with their ability to serve as scaffolds having unique chemical, optical and magnetic properties, offer the promise of merging diagnostic medicine with material engineering. Such nanoparticles can interact preferentially with proteases enriched in tumors, providing the ability to assess disease state in a noninvasive and spatiotemporal manner. We review recent advances in the development of nanoparticles for imaging and quantification of proteolytic activity in tumor models, and prognosticate future advancements.
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Affiliation(s)
- Tareq Anani
- Department of Chemical Engineering, Samuel Ginn College of Engineering, 212 Ross Hall, Auburn University, Auburn, AL 36849, USA
| | - Peter Panizzi
- Department of Drug Discovery & Development, Harrison School of Pharmacy, 4306 Walker Building, Auburn University, Auburn, AL 36849, USA
| | - Allan E. David
- Department of Chemical Engineering, Samuel Ginn College of Engineering, 212 Ross Hall, Auburn University, Auburn, AL 36849, USA
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16
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Zhang D, Jia H, Wang Y, Li WM, Hou YC, Yin SW, Wang TD, He SX, Lu SY. A CD44 specific peptide developed by phage display for targeting gastric cancer. Biotechnol Lett 2015; 37:2311-20. [PMID: 26140900 DOI: 10.1007/s10529-015-1896-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 06/23/2015] [Indexed: 01/14/2023]
Abstract
OBJECTIVE To develop a peptide probe that could be used for gastric cancer detection via binding to CD44 protein with specificity and affinity. RESULTS A 12-mer phage peptide library was screened against immobilized CD44 protein. Bound phage counts using ELISA were performed to identify phage clones carrying the most highly selective peptide, which termed RP-1. Immunofluorescence and flow cytometry analysis indicated that the consensus peptide RP-1 could bind to CD44-positive gastric cancer cells with mean fluorescence intensities significantly higher than that of CD44-negative cells. CD44 knockdown led to decreased binding activity of RP-1 to the same cell line. Tissue array technique was used to identify the relationship (r = 0.556) between peptide binding and CD44 detection on gastric cancer tissues. Further, the hyaluronan-binding domain of CD44 was docked with RP-1 using computer modeling/docking approaches, revealing a RP-1/CD44 interaction with geometrical and energy match (-8.6 kcal/mol). CONCLUSIONS The RP-1 peptide we screened exhibits affinity and specificity to CD44 on cells and has the potential to be used as a candidate probe for gastric cancer cell targeting.
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Affiliation(s)
- Dan Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Medical School, Xian Jiaotong University, Xi'an, 710061, China.
| | - Huan Jia
- Department of General Surgery, The First Affiliated Hospital of Xi'an Medical University, Xi'an, 710077, Shaanxi, China.
| | - Yan Wang
- Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi, China.
| | - Wei-Ming Li
- Department of General Surgery, The First Affiliated Hospital of Medical School, Xian Jiaotong University, Xi'an, 710061, Shaanxi, China.
| | - Ying-Chun Hou
- College of Life Science, Shaanxi Normal University, Xi'an, 710119, Shaanxi, China.
| | - Shi-Wei Yin
- College of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, 710119, Shaanxi, China.
| | - Thomas D Wang
- Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of Michigan Ann Arbor, Ann Arbor, MI, 48109, USA.
| | - Shui-Xiang He
- Department of Gastroenterology, The First Affiliated Hospital of Medical School, Xian Jiaotong University, Xi'an, 710061, China.
| | - Shao-Ying Lu
- Department of General Surgery, The First Affiliated Hospital of Medical School, Xian Jiaotong University, Xi'an, 710061, Shaanxi, China.
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17
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Barsanti C, Lenzarini F, Kusmic C. Diagnostic and prognostic utility of non-invasive imaging in diabetes management. World J Diabetes 2015; 6:792-806. [PMID: 26131322 PMCID: PMC4478576 DOI: 10.4239/wjd.v6.i6.792] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 12/23/2014] [Accepted: 04/14/2015] [Indexed: 02/05/2023] Open
Abstract
Medical imaging technologies are acquiring an increasing relevance to assist clinicians in diagnosis and to guide management and therapeutic treatment of patients, thanks to their non invasive and high resolution properties. Computed tomography, magnetic resonance imaging, and ultrasonography are the most used imaging modalities to provide detailed morphological reconstructions of tissues and organs. In addition, the use of contrast dyes or radionuclide-labeled tracers permits to get functional and quantitative information about tissue physiology and metabolism in normal and disease state. In recent years, the development of multimodal and hydrid imaging techniques is coming to be the new frontier of medical imaging for the possibility to overcome limitations of single modalities and to obtain physiological and pathophysiological measurements within an accurate anatomical framework. Moreover, the employment of molecular probes, such as ligands or antibodies, allows a selective in vivo targeting of biomolecules involved in specific cellular processes, so expanding the potentialities of imaging techniques for clinical and research applications. This review is aimed to give a survey of characteristics of main diagnostic non-invasive imaging techniques. Current clinical appliances and future perspectives of imaging in the diagnostic and prognostic assessment of diabetic complications affecting different organ systems will be particularly addressed.
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18
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Madru R, Svenmarker P, Ingvar C, Ståhlberg F, Engels SA, Knutsson L, Strand SE. Development of a Hybrid Nanoprobe for Triple-Modality MR/SPECT/Optical Fluorescence Imaging. Diagnostics (Basel) 2014; 4:13-26. [PMID: 26852675 PMCID: PMC4665510 DOI: 10.3390/diagnostics4010013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 02/28/2014] [Accepted: 03/04/2014] [Indexed: 12/02/2022] Open
Abstract
Hybrid clinical imaging is an emerging technology, which improves disease diagnosis by combining already existing technologies. With the combination of high-resolution morphological imaging, i.e., MRI/CT, and high-sensitive molecular detection offered by SPECT/PET/Optical, physicians can detect disease progression at an early stage and design patient-specific treatments. To fully exploit the possibilities of hybrid imaging a hybrid probe compatible with each imaging technology is required. Here, we present a hybrid nanoprobe for triple modality MR/SPECT/Fluorescence imaging. Our imaging agent is comprised of superparamagnetic iron oxide nanoparticles (SPIONs), labeled with 99mTc and an Alexa fluorophore (AF), together forming 99mTc-AF-SPIONs. The agent was stable in human serum, and, after subcutaneous injection in the hind paw of Wistar rats, showed to be highly specific by accumulating in the sentinel lymph node. All three modalities clearly visualized the imaging agent. Our results show that a single imaging agent can be used for hybrid imaging. The use of a single hybrid contrast agent permits simultaneous hybrid imaging and, more conventionally, allow for single modality imaging at different time points. For example, a hybrid contrast agent enables pre-operative planning, intra-operative guidance, and post-operative evaluation with the same contrast agent.
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Affiliation(s)
- Renata Madru
- Department of Medical Radiation Physics, Lund University, Barngatan 2, 221 85 Lund, Sweden.
| | - Pontus Svenmarker
- Department of Physics, Lund University, Professorsgatan 1, 223 63 Lund, Sweden.
| | - Christian Ingvar
- Department of Surgery, Skane University Hospital, Entrégatan 7, 221 85 Lund, Sweden.
| | - Freddy Ståhlberg
- Department of Medical Radiation Physics, Lund University, Barngatan 2, 221 85 Lund, Sweden.
- Lund University Bioimaging Center (LBIC), Kliniggatan 32, 222 42 Lund, Sweden.
- Department of Radiology, Skane University Hospital, Entrégatan 7, 221 85 Lund, Sweden.
| | | | - Linda Knutsson
- Department of Medical Radiation Physics, Lund University, Barngatan 2, 221 85 Lund, Sweden.
| | - Sven-Erik Strand
- Department of Medical Radiation Physics, Lund University, Barngatan 2, 221 85 Lund, Sweden.
- Lund University Bioimaging Center (LBIC), Kliniggatan 32, 222 42 Lund, Sweden.
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19
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Desar IME, Gilles R, van Herpen CML, Timmer-Bonte AJNH, Cantarini MV, van der Graaf WTA, Oyen WJG. (18)F-FLT-PET for Response Evaluation of MEK Inhibitor Selumetinib (AZD6244, ARRY-142886) in Patients with Solid Tumors. World J Nucl Med 2013; 11:65-9. [PMID: 23372439 PMCID: PMC3555396 DOI: 10.4103/1450-1147.103413] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Selumetinib (AZD6244, ARRY-142886) is a potent, selective, uncompetitive inhibitor of MEK 1 / 2, part of the RAF/MEK/ERK protein kinase signal cascade, which is responsible for tumor. This pilot study was used to explore if (18)F-fluoro-l-thymidine (FLT), a thymidine analogue positron emission tomography (PET) tracer and a surrogate marker for proliferation, can be used as an early predictor of response for patients with solid cancers treated with Selumetinib. FLT-PET scans were performed in four patients at baseline and after 2 weeks of treatment with Selumetinib. FLT uptake in tumors was analyzed qualitatively and quantitatively by measuring standard uptake value (SUV) max in regions of interest (ROI). Results were compared to computed tomography (CT) scans (baseline and after 8 weeks), which were evaluated using the response evaluation criteria in solid tumors (RECIST) 1.0 criteria. One patient with melanoma showed both a qualitative and quantitative decrease in FLT uptake associated with a decrease in sum of longest diameter of 12% RECIST on CT evaluation. Another patient who had colorectal carcinoma (CRC) showed a significant increase in FLT uptake with initially stable, but eventually progressive disease on CT. The other two patients (one with melanoma and one with CRC) showed no significant changes in FLT uptake, whereas CT evaluation showed progressive disease. This is the first report describing changes in FLT-PET in patients receiving Selumetinib. In two patients, changes in FLT uptake as early as after 2 weeks of treatment were consistent with CT results after 8 weeks. Biomarkers to predict and evaluate treatment the outcome of targeted therapies are highly warranted. These initial results need further investigation.
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Affiliation(s)
- Ingrid M E Desar
- Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
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20
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LEE MYOUNGWOO, KIM HYEJIN, YOO KEONHEE, KIM DAESEONG, YANG JINMO, KIM HYERYUNG, NOH YOOHUN, BAEK HYUNJUNG, KWON HEECHUNG, SON MEONGHI, LEE SOOHYUN, CHEUH HEEWON, JUNG HYELIM, SUNG KIWOONG, KOO HONGHOE. Establishment of a bioluminescent imaging-based in vivo leukemia model by intra-bone marrow injection. Int J Oncol 2012; 41:2047-56. [DOI: 10.3892/ijo.2012.1634] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 07/23/2012] [Indexed: 11/06/2022] Open
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21
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Stacy MR, Maxfield MW, Sinusas AJ. Targeted molecular imaging of angiogenesis in PET and SPECT: a review. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 2012; 85:75-86. [PMID: 22461745 PMCID: PMC3313541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Over the past few decades, there have been significant advancements in the imaging techniques of positron emission tomography (PET) and single photon emission tomography (SPECT). These changes have allowed for the targeted imaging of cellular processes and the development of hybrid imaging systems (e.g., SPECT/CT and PET/CT), which provide both functional and structural images of biological systems. One area that has garnered particular attention is angiogenesis as it relates to ischemic heart disease and limb ischemia. Though the aforementioned techniques have benefits and consequences, they enable scientists and clinicians to identify regions that are vulnerable to or have been exposed to ischemic injury via non-invasive means. This literature review highlights the advancements in molecular imaging techniques and specific probes as they pertain to the process of angiogenesis in cardiovascular disease.
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Affiliation(s)
- Mitchel R. Stacy
- Section of Cardiovascular Medicine, Department of
Internal Medicine, Yale School of Medicine, New Haven, Connecticut,To whom all correspondence should be
addressed: Mitchel R. Stacy, Nuclear Cardiology, 3 FMP, PO Box 208017, New
Haven, CT 06520-8017, Tel: 203-737-5917; Fax: 203-737-1030;
| | - Mark W. Maxfield
- Department of Surgery, Yale School of Medicine, New
Haven, Connecticut
| | - Albert J. Sinusas
- Section of Cardiovascular Medicine, Department of
Internal Medicine, Yale School of Medicine, New Haven, Connecticut,Department of Diagnostic Radiology, Yale School of
Medicine, New Haven, Connecticut
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22
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Cook N, Jodrell DI, Tuveson DA. Predictive in vivo animal models and translation to clinical trials. Drug Discov Today 2012; 17:253-60. [PMID: 22493784 DOI: 10.1016/j.drudis.2012.02.003] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Vast resources are expended during the development of new cancer therapeutics, and selection of optimal in vivo models should improve this process. Genetically engineered mouse models (GEMM) of cancer have progressively improved in technical sophistication and, accurately recapitulating the human cognate condition, have had a measureable impact on our knowledge of tumourigenesis. However, the application of GEMMs to facilitate the development of innovative therapeutic and diagnostic approaches has lagged behind. GEMMs that recapitulate human cancer offer an additional opportunity to accelerate drug development, and should complement the role of the widely used engraftment tumour models.
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Affiliation(s)
- Natalie Cook
- Cancer Research UK, Cambridge Research Institute, UK.
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23
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Sinusas AJ, Thomas JD, Mills G. The future of molecular imaging. JACC Cardiovasc Imaging 2011; 4:799-806. [PMID: 21757172 DOI: 10.1016/j.jcmg.2011.05.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2011] [Revised: 05/01/2011] [Accepted: 05/05/2011] [Indexed: 11/17/2022]
Affiliation(s)
- Albert J Sinusas
- Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
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24
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Kobayashi H, Longmire MR, Ogawa M, Choyke PL. Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals. Chem Soc Rev 2011; 40:4626-48. [PMID: 21607237 PMCID: PMC3417232 DOI: 10.1039/c1cs15077d] [Citation(s) in RCA: 154] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references).
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Affiliation(s)
- Hisataka Kobayashi
- Molecular Imaging Program, National Cancer Institute/NIH, Bldg. 10, Room B3B69, MSC 1088, 10 Center Dr Bethesda, Maryland 20892-1088, USA.
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