|
1
|
Pan Q, Xu H, Liu S, Zhang H, Zhang S, Li J, Li F, Luo Y. Head-to-Head Comparison of 68Ga-FAPI-04 and 18F-FDG PET/CT for the Assessment of Crohn's Disease: A Prospective Pilot Study. Clin Nucl Med 2025:00003072-990000000-01634. [PMID: 40173312 DOI: 10.1097/rlu.0000000000005815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 02/02/2025] [Indexed: 04/04/2025]
Abstract
BACKGROUND Crohn disease is a chronic granulomatous inflammatory disease of gastrointestinal tract. Previous studies showed Crohn disease strictures overexpress fibroblast activation protein and had active 68Ga-FAPI-04 uptake. Our study was to compare the diagnostic performance of 68Ga-FAPI-04 and 18F-FDG PET/CT in Crohn disease. PATIENTS AND METHODS This is a prospective cohort study recruiting patients with newly diagnosed or relapsed Crohn disease. All the patients underwent 68Ga-FAPI-04 and 18F-FDG PET/CT. The diagnostic performance of the 2 PET/CT modalities and their uptake values were compared. The correlation of PET semiquantitative parameters [metabolic intestinal volume (MIVFDG and MIVFAPI), total intestinal uptake (TIUFDG and TIUFAPI)] with clinical biomarkers were also analyzed. RESULTS Seventeen participants (13 men and 4 women, age 32.3 ± 15.9 y) were recruited. The sensitivity of 68Ga-FAPI-04 and 18F-FDG PET/CT in detecting Crohn lesions were 90.0% and 85.0%, and the specificities were 93.0% and 88.4%, respectively. In receiver operating characteristic curve analysis, 68Ga-FAPI-04 PET/CT [area under the curve = 0.92 (95% CI: 0.83-0.97), P < 0.001] showed better diagnostic performance compared with 18F-FDG PET/CT [area under the curve = 0.87 (95% CI: 0.78-0.93), P < 0.001; P = 0.043]. The SUVmax of 68Ga-FAPI and 18F-FDG in stricture/fistula lesions were significantly higher than those in non-stricture/fistula lesions (68Ga-FAPI, 10.9 ± 6.7 vs 5.0 ± 3.5, P = 0.0002; 18F-FDG, 9.5 ± 4.9 vs 5.3 ± 1.8, P = 0.0016). TIUFAPI and MIVFAPI of 68Ga-FAPI-04 PET/CT were significantly correlated with high sensitivity C-reactive protein and simple endoscopic score for Crohn disease (P < 0.05). TIUFDG and MIVFDG of 18F-FDG PET/CT were also correlated with simple endoscopic scores for Crohn disease (P < 0.05). CONCLUSIONS 68Ga-FAPI-04 PET/CT showed better diagnostic performance than 18F-FDG PET/CT in Crohn disease.
Collapse
Affiliation(s)
- Qingqing Pan
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- State Key Laboratory of Common Mechanism Research for Major Diseases
| | - Hui Xu
- Department of Gastroenterology, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Dongcheng, Beijing, P.R. China
| | - Silu Liu
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- State Key Laboratory of Common Mechanism Research for Major Diseases
| | - Hongzhe Zhang
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- State Key Laboratory of Common Mechanism Research for Major Diseases
| | - Shengyu Zhang
- Department of Gastroenterology, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Dongcheng, Beijing, P.R. China
| | - Ji Li
- Department of Gastroenterology, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Dongcheng, Beijing, P.R. China
| | - Fang Li
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- State Key Laboratory of Common Mechanism Research for Major Diseases
| | - Yaping Luo
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- State Key Laboratory of Common Mechanism Research for Major Diseases
| |
Collapse
|
|
2
|
Salehi Farid A, Rowley JE, Allen HH, Kruger IG, Tavakolpour S, Neeley K, Cong M, Shahbazian H, Dorafshani N, Berrada A, MacDonagh AC, Padera RF, Brugarolas P, Packard AB, Rosenbaum MW, Divakaran S, Di Carli MF, Rashidian M. CD45-PET is a robust, non-invasive tool for imaging inflammation. Nature 2025; 639:214-224. [PMID: 39843738 DOI: 10.1038/s41586-024-08441-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 11/21/2024] [Indexed: 01/24/2025]
Abstract
Imaging inflammation holds immense potential for advancing the diagnosis, treatment and prognosis of many conditions1-3. The lack of a specific and sensitive positron emission tomography (PET) probe to detect inflammation is a critical challenge. To bridge this gap, we present CD45-PET imaging, which detects inflammation with exceptional sensitivity and clarity in several preclinical models. Notably, the intensity of the CD45-PET signal correlates robustly with the severity of disease in models of inflammatory lung and bowel diseases, outperforming 18F-fluorodeoxyglucose PET, the most widely used imaging modality for inflammation globally. Longitudinal CD45-PET imaging further enables precise monitoring of dynamic changes in tissue-specific inflammatory profiles. Finally, we developed a human CD45-PET probe for clinical translation that effectively detects human immune cells in a humanized mouse model. CD45-PET imaging holds substantial clinical promise, offering a tool for guiding diagnostic and therapeutic decisions for inflammatory diseases through a precise, whole-body assessment of the inflammation profiles of individual patients.
Collapse
Affiliation(s)
- Ali Salehi Farid
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Jennifer E Rowley
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Harris H Allen
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Isabella G Kruger
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Soheil Tavakolpour
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Kyle Neeley
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Min Cong
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Haneyeh Shahbazian
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Niki Dorafshani
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Achraf Berrada
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
| | | | - Robert F Padera
- Harvard Medical School, Boston, MA, USA
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
| | - Pedro Brugarolas
- Harvard Medical School, Boston, MA, USA
- Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
| | - Alan B Packard
- Harvard Medical School, Boston, MA, USA
- Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Boston Children's Hospital, Boston, MA, USA
| | - Matthew W Rosenbaum
- Harvard Medical School, Boston, MA, USA
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Sanjay Divakaran
- Harvard Medical School, Boston, MA, USA
- Cardiovascular Imaging Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Cardiovascular Imaging Program, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Marcelo F Di Carli
- Harvard Medical School, Boston, MA, USA
- Cardiovascular Imaging Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Cardiovascular Imaging Program, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Mohammad Rashidian
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
- Harvard Medical School, Boston, MA, USA.
- Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| |
Collapse
|
|
3
|
Gao CY, Pan YJ, Su WS, Wu CY, Chang TY, Yang FY. Abdominal ultrasound stimulation alleviates DSS-induced colitis and behavioral disorders in mice by mediating the microbiota-gut-brain axis balance. Neurotherapeutics 2025; 22:e00494. [PMID: 39580323 DOI: 10.1016/j.neurot.2024.e00494] [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: 08/02/2024] [Revised: 10/17/2024] [Accepted: 11/14/2024] [Indexed: 11/25/2024] Open
Abstract
Inflammatory bowel disease (IBD) has the potential to induce neuroinflammation, which may increase the risk of developing neurodegenerative disorders. Ultrasound stimulation to the abdomen is a potential treatment for dextran sulfate sodium (DSS)-induced acute colitis. The present study aimed to investigate whether abdominal low-intensity pulsed ultrasound (LIPUS) can alleviate DSS-induced neuroinflammation through the microbiota-gut-brain axis. Male mice were fed DSS to induce ulcerative colitis. LIPUS stimulation was then applied to the abdomen at intensities of 0.5 and 1.0 W/cm2. Mouse biological samples were analyzed, and behavior was evaluated. [18F]FEPPA PET/CT imaging was employed to track and quantify inflammation in the abdomen and brain. Changes in the gut microbiota composition were analyzed using 16S rRNA sequencing. Abdominal LIPUS significantly inhibited the DSS-induced inflammatory response, repaired destroyed crypts, and partially preserved the epithelial barrier. [18F]FEPPA accumulation in the colitis-induced neuroinflammation in the abdomen and specific brain regions significantly decreased after LIPUS treatment. LIPUS maintained intestinal integrity by increasing zonula occludens and occludin levels, reduced lipopolysaccharide-binding protein and lipopolysaccharide levels in the serum, and improved behavioral dysfunctions. Moreover, LIPUS, at an intensity of 0.5 W/cm2, reshaped the gut microbiota in colitis-induced mice by increasing the relative abundance of the Firmicutes and decreasing the relative abundance of the Bacteroidota. Our findings demonstrated that abdominal LIPUS stimulation has the potential to be a novel therapeutic strategy to improve colitis-induced behavioral disorders through microbiota-gut-brain axis signaling.
Collapse
Affiliation(s)
- Cong-Yong Gao
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Ju Pan
- Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan City, Taiwan
| | - Wei-Shen Su
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Yi Wu
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ting-Yu Chang
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Feng-Yi Yang
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| |
Collapse
|
|
4
|
Choi JH, Park YJ, Lee H, Kwon HR, Oh J, Lim CH, Han EJ, Choi JY. 18F-FDG PET/CT in Inflammation and Infection: Procedural Guideline by the Korean Society of Nuclear Medicine. Nucl Med Mol Imaging 2025; 59:27-40. [PMID: 39881970 PMCID: PMC11772639 DOI: 10.1007/s13139-024-00894-x] [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: 10/02/2024] [Revised: 11/13/2024] [Accepted: 11/14/2024] [Indexed: 01/03/2025] Open
Abstract
Abstract This guideline outlines the use of 18F-fluoro-2-deoxyglucose positron emission tomography / computed tomography for the diagnosis and management of infectious and inflammatory diseases. It provides detailed recommendations for healthcare providers on patient preparation, imaging procedures, and the interpretation of results. Adapted from international standards and tailored to local clinical practices, the guideline emphasizes safety, quality control, and effective use of the technology in various conditions, including spinal infections, diabetic foot, osteomyelitis, vasculitis, and cardiac inflammation. The aim is to assist nuclear medicine professionals in delivering accurate diagnoses and improving patient outcomes while allowing flexibility to adapt to individual patient needs, technological advancements, and evolving medical knowledge. This document is a comprehensive resource for enhancing the quality and safety of 18F-fluoro-2-deoxyglucose positron emission tomography / computed tomography for the evaluation of infectious and inflammatory diseases. Preamble The Korean Society of Nuclear Medicine (KSNM) was established in 1961 to promote the clinical and technological advancement of nuclear medicine in South Korea, with members that include nuclear medicine physicians and associated scientists. The KSNM regularly formulates and revises procedural guidelines for nuclear medicine examinations to enhance the field and improve the quality of patient care. These guidelines are designed to support healthcare professionals in providing appropriate medical care to patients. However, they are not immutable rules or mandatory requirements for conducting examinations.Therefore, KSNM states that these guidelines should not be used in legal actions challenging a healthcare professional's medical decisions. The ultimate judgment regarding specific procedures or appropriate measures should be made by nuclear medicine physicians, considering the unique circumstances of each case. Deviation from these guidelines does not imply substandard medical practice. Rather, reasonable judgments differing from the guidelines can be made based on the patient's condition, available resources, and advancements in knowledge or technology. Due to the diversity and complexity of patients, it is often challenging to predict the most appropriate diagnostic and accurate therapeutic responses. Thus, adherence to these guidelines does not always guarantee an exact diagnosis or successful outcomes.The purpose of this guideline is to assist healthcare providers in making reasonable decisions and conducting effective and safe examinations based on current medical knowledge, available resources, and patient needs when performing 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) examinations for infectious/inflammatory diseases.
Collapse
Affiliation(s)
- Joon Ho Choi
- Department of Nuclear Medicine, Soonchunhyang University Hospital Bucheon, Bucheon, Republic of Korea
| | - Yong-Jin Park
- Department of Nuclear Medicine, Ajou University Medical Center, Ajou University School of Medicine, Suwon, Republic of Korea
- Department of Medical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea
| | - Hyunjong Lee
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351 Republic of Korea
| | - Hye Ryeong Kwon
- Department of Nuclear Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
| | - Jinkyoung Oh
- Department of Nuclear Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chae Hong Lim
- Department of Nuclear Medicine, Soonchunhyang University Hospital Seoul, Seoul, Republic of Korea
| | - Eun Ji Han
- Department of Nuclear Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Joon Young Choi
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351 Republic of Korea
| | - The Korean Society of Nuclear Medicine Medical Affairs Committee
- Department of Nuclear Medicine, Soonchunhyang University Hospital Bucheon, Bucheon, Republic of Korea
- Department of Nuclear Medicine, Ajou University Medical Center, Ajou University School of Medicine, Suwon, Republic of Korea
- Department of Medical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351 Republic of Korea
- Department of Nuclear Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
- Department of Nuclear Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Nuclear Medicine, Soonchunhyang University Hospital Seoul, Seoul, Republic of Korea
- Department of Nuclear Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| |
Collapse
|
|
5
|
Bhattaru A, Pundyavana A, Raynor W, Chinta S, Werner TJ, Alavi A. 18F-FDG-PET and other imaging modalities in the diagnosis and management of inflammatory bowel disease. AMERICAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 2024; 14:295-305. [PMID: 39583912 PMCID: PMC11578808 DOI: 10.62347/yxqt2560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 08/22/2024] [Indexed: 11/26/2024]
Abstract
Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory condition of the gastrointestinal (GI) tract that presents complex diagnostic and management challenges. Early detection and treatment of IBD is paramount, as IBD can present with serious complications, including bowel perforation, arthritis, and colorectal cancer. Most forms of diagnosis and therapeutic management, like ileocolonoscopy and upper endoscopy are highly invasive and require extensive preparation at great discomfort to patients. 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging can be a potential solution to the current limitations in imaging for IBD. This review explores the utility and limitations of various imaging modalities used to detect and manage IBD including ileocolonoscopy, magnetic resonance enterography (MRE), gastrointestinal ultrasound (IUS), and 18F-FDG-PET/computed tomography (18F-FDG-PET/CT) and magnetic resonance imaging (18F-FDG-PET/MR). This review has an emphasis on PET imaging and highlights its benefits in detection, management, and monitoring therapeutic response of UC and CD.
Collapse
Affiliation(s)
- Abhijit Bhattaru
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
- Department of Medicine, Rutgers New Jersey Medical SchoolNewark, New Jersey, The United States
| | - Anish Pundyavana
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
- Department of Medicine, Rutgers New Jersey Medical SchoolNewark, New Jersey, The United States
| | - William Raynor
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
| | - Sree Chinta
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
- Department of Medicine, Rutgers New Jersey Medical SchoolNewark, New Jersey, The United States
| | - Thomas J Werner
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
| | - Abass Alavi
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
| |
Collapse
|
|
6
|
Lin CY, Chang MC, Kao CH. Comparing the Diagnostic Value of FDG PET or PET/CT With FDG PET/MR in Inflammatory Bowel Disease-A Systematic Review and Meta-analysis. Clin Nucl Med 2024; 49:e492-e500. [PMID: 38973081 DOI: 10.1097/rlu.0000000000005379] [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: 07/09/2024]
Abstract
BACKGROUND The aim of this study was to compare the diagnostic value of 18 F-FDG PET or PET/CT with FDG PET/MR in patients with inflammatory bowel disease (IBD). METHODS A comprehensive search was performed in PubMed for studies reporting the diagnostic performance of FDG PET (PET/CT) and FDG PET/MR in IBD from the inception of the database to March 14, 2024, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Fourteen studies were included in this systematic review and meta-analysis. Pooled estimates of segment-based sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for FDG PET (PET/CT) and FDG PET/MR were calculated alongside 95% confidence intervals. Summary receiver operating characteristic (SROC) curves were plotted, and the area under the SROC curve was determined alongside the Q * index. RESULTS The segment-based pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the SROC curve of FDG PET (PET/CT) for diagnosing IBD (9 studies) were 0.81, 0.86, 5.76, 0.22, 31.92, and 0.92, respectively. Those of FDG PET/MR (5 studies) were 0.78, 0.92, 10.97, 0.25, 51.79, and 0.95. There was no significant difference in the abilities of detecting or excluding IBD between FDG PET (PET/CT) and FDG PET/MR. CONCLUSIONS For diagnostic value in patients with IBD, there was no significant difference between FDG PET (PET/CT) and FDG PET/MR. Both FDG PET (PET/CT) and FDG PET/MR have demonstrated high diagnostic performance for accurate diagnosing in patients with IBD.
Collapse
Affiliation(s)
- Chun-Yi Lin
- From the Department of Nuclear Medicine, Changhua Christian Hospital, Changhua
| | - Ming-Che Chang
- From the Department of Nuclear Medicine, Changhua Christian Hospital, Changhua
| | | |
Collapse
|
|
7
|
Bhowmik AA, Heikkilä TRH, Polari L, Virta J, Liljenbäck H, Moisio O, Li XG, Viitanen R, Jalkanen S, Koffert J, Toivola DM, Roivainen A. Detection of Intestinal Inflammation by Vascular Adhesion Protein-1-Targeted [ 68Ga]Ga-DOTA-Siglec-9 Positron Emission Tomography in Murine Models of Inflammatory Bowel Disease. Mol Imaging Biol 2024; 26:322-333. [PMID: 38110791 DOI: 10.1007/s11307-023-01885-8] [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: 09/29/2023] [Revised: 12/01/2023] [Accepted: 12/04/2023] [Indexed: 12/20/2023]
Abstract
PURPOSE Inflammatory bowel disease (IBD) can be imaged with positron emission tomography (PET), but existing PET radiopharmaceuticals have limited diagnostic accuracy. Vascular adhesion protein-1 (VAP-1) is an endothelial cell surface molecule that controls leukocyte extravasation into sites of inflammation. However, the role of inflammation-induced VAP-1 expression in IBD is still unclear. Therefore, this study investigated the utility of VAP-1-targeted [68Ga]Ga-DOTA-Siglec-9 positron emission tomography/computed tomography (PET/CT) for assessing inflammation in two mouse models of IBD. PROCEDURES Studies were performed using K8-/- mice that develop a chronic colitis-phenotype and C57Bl/6NCrl mice with acute intestinal inflammation chemically-induced using 2.5% dextran sodium sulfate (DSS) in drinking water. In both diseased and control mice, uptake of the VAP-1-targeting peptide [68Ga]Ga-DOTA-Siglec-9 was assessed in intestinal regions of interest using in vivo PET/CT, after which ex vivo gamma counting, digital autoradiography, and histopathological analyses were performed. Immunofluorescence staining was performed to determine VAP-1-expression in the intestine, including in samples from patients with ulcerative colitis. RESULTS Intestinal inflammation could be visualized by [68Ga]Ga-DOTA-Siglec-9 PET/CT in two murine models of IBD. In both models, the in vivo PET/CT and ex vivo studies of [68Ga]Ga-DOTA-Siglec-9 uptake were significantly higher than in control mice. The in vivo uptake was increased on average 1.4-fold in the DSS model and 2.0-fold in the K8-/- model. Immunofluorescence staining revealed strong expression of VAP-1 in the inflamed intestines of both mice and patients. CONCLUSIONS This study suggests that the VAP-1-targeting [68Ga]Ga-DOTA-Siglec-9 PET tracer is a promising tool for non-invasive imaging of intestinal inflammation. Future studies in patients with IBD and evaluation of the potential value of [68Ga]Ga-DOTA-Siglec-9 in diagnosis and monitoring of the disease are warranted.
Collapse
Affiliation(s)
- Achol A Bhowmik
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland
| | - Taina R H Heikkilä
- Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland
- InFLAMES Research Flagship, Åbo Akademi University, Turku, Finland
| | - Lauri Polari
- Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland
- InFLAMES Research Flagship, Åbo Akademi University, Turku, Finland
| | - Jenni Virta
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland
| | - Heidi Liljenbäck
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland
- Turku Center for Disease Modelling, University of Turku, Turku, Finland
| | - Olli Moisio
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland
| | - Xiang-Guo Li
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland
- Department of Chemistry, University of Turku, Turku, Finland
- InFLAMES Research Flagship, University of Turku, Turku, Finland
| | - Riikka Viitanen
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland
| | - Sirpa Jalkanen
- InFLAMES Research Flagship, University of Turku, Turku, Finland
- MediCity Research Laboratory, University of Turku, Turku, Finland
| | - Jukka Koffert
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland
- InFLAMES Research Flagship, University of Turku, Turku, Finland
- Department of Gastroenterology, Turku University Hospital, Turku, Finland
| | - Diana M Toivola
- Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland
- InFLAMES Research Flagship, Åbo Akademi University, Turku, Finland
- Turku Center for Disease Modelling, University of Turku, Turku, Finland
| | - Anne Roivainen
- Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland.
- Turku Center for Disease Modelling, University of Turku, Turku, Finland.
- InFLAMES Research Flagship, University of Turku, Turku, Finland.
- Turku PET Centre, Turku University Hospital, Turku, Finland.
| |
Collapse
|
|
8
|
Li N, Ye Y, Wu Y, Li L, Hu J, Luo D, Li Y, Yang J, Gao Y, Hai W, Xie Y, Jiang L. Alterations in histology of the aging salivary gland and correlation with the glandular inflammatory microenvironment. iScience 2023; 26:106571. [PMID: 37124415 PMCID: PMC10131127 DOI: 10.1016/j.isci.2023.106571] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 12/29/2022] [Accepted: 03/28/2023] [Indexed: 05/02/2023] Open
Abstract
Aging-related salivary dysfunction typically causes reduced saliva volumes, which leads to debilitating consequences, even affecting patient quality of life. Understanding the respective clinicopathological characteristics and molecular mechanisms underlying salivary gland functioning during aging is vital for therapeutic purposes. Here, we provide a detailed atlas of the salivary gland microenvironment during aging, and we identified several phenotypes characteristic of aging salivary glands, including acini atrophy, increased inflammatory cells, altered immune responses, and accumulation of lysosomes and autophagosomes in aging cells, which may reflect progressive degeneration of salivary gland function. Furthermore, our analyses suggested significant enrichment of metabolic pathways in aging glands. Our results revealed complex cellular cross-talk among aging acinar cells, inflammatory factors, and immune responses. A natural aging animal model was established to verify these findings. This study provides mechanistic insights into age-related clinicopathogenesis, important implications for early diagnosis, and identification of new targets for improving salivary gland dysfunction.
Collapse
Affiliation(s)
- Ning Li
- Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
| | - Yulin Ye
- Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
| | - Yicheng Wu
- Core Facility of Basic Medical Sciences, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Lei Li
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiawei Hu
- Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
| | - Danyang Luo
- Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
| | - Yusi Li
- Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
| | - Jie Yang
- Core Facility of Basic Medical Sciences, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Yiming Gao
- Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
| | - Wangxi Hai
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Corresponding author
| | - Yinyin Xie
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Corresponding author
| | - Liting Jiang
- Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- Corresponding author
| |
Collapse
|
|
9
|
Zhang L, Wang Y, Homan KT, Gaudette SM, McCluskey AJ, Chan Y, Murphy J, Abdalla M, Nelson CM, Sun VZ, Erickson JE, Knight HL, Clabbers A, Sterman AJS, Mitra S. Imaging the Alternatively Spliced D Domain of Tenascin C in a Preclinical Model of Inflammatory Bowel Disease. Mol Imaging Biol 2023; 25:314-323. [PMID: 35906512 PMCID: PMC10006278 DOI: 10.1007/s11307-022-01758-6] [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: 04/20/2022] [Revised: 07/11/2022] [Accepted: 07/12/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE To image colon-expressed alternatively spliced D domain of tenascin C in preclinical colitis models using near infrared (NIR)-labeled targeted molecular imaging agents. PROCEDURES A human IgG1 with nanomolar binding affinity specific to the alternatively spliced D domain of tenascin C was generated. Immunohistochemistry identified disease-specific expression of this extracellular matrix protein in the colon of mice given dextran sulfate sodium in the drinking water. The antibody reagent was labeled with the NIR fluorophore IRDye 800CW via amine chemistry and intravenously dosed to evaluate in vivo targeting specificity. Increasing doses of imaging agent were given to estimate the saturating dose. RESULTS The NIR-labeled proteins successfully targeted colonic lesions in a murine model of colitis. Co-administration of a molar excess competing unlabeled dose reduced normalized uptake in diseased colon by > 70%. Near infrared ex vivo images of colon resected from diseased animals showed saturation at doses exceeding 1 nmol and was confirmed with additional quantitative ex vivo biodistribution. Cellular-level specificity and protein stability were assessed via microscopy. CONCLUSIONS Our imaging data suggest the alternatively spliced D domain of tenascin C is a promising target for delivery-based applications in inflammatory bowel diseases.
Collapse
Affiliation(s)
- Liang Zhang
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA.
| | - Yuzhen Wang
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA
| | | | - Stephanie M Gaudette
- Worcester Technical High School, 1 Officer Manny Familia Wy, Worcester, MA, 01605, USA
| | | | - Ying Chan
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA
| | - Joanne Murphy
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA
| | - Mary Abdalla
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA
| | | | - Victor Z Sun
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA
| | - Jamie E Erickson
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA
| | - Heather L Knight
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA
| | - Anca Clabbers
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA
| | | | - Soumya Mitra
- AbbVie Bioresearch Center, 100 Research Dr, Worcester, MA, 01605, USA
| |
Collapse
|
|
10
|
Dalby S, Skallerup S, Baun C, Christensen LG, Rathe M, Palner M, Husby S, Moeller JB. PET/CT imaging detects intestinal inflammation in a mouse model of doxorubicin-induced mucositis. Front Oncol 2022; 12:1061804. [PMID: 36591502 PMCID: PMC9798215 DOI: 10.3389/fonc.2022.1061804] [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: 10/05/2022] [Accepted: 12/01/2022] [Indexed: 12/23/2022] Open
Abstract
Introduction A severe side effect of cancer chemotherapy is the development of gastrointestinal mucositis, characterised by mucosal inflammation. We investigated if 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography combined with computed tomography (2-[18F]FDG-PET/CT) could visualise gastrointestinal mucositis in mice treated with the chemotherapeutic agent doxorubicin. Methods In this study, gastrointestinal inflammation was longitudinally evaluated by 2-[18F]FDG-PET/CT scans before and 1, 3, 6, and 10 days after treatment with doxorubicin. Doxorubicin-treated mice were compared to saline-treated littermates using the abdominal standard uptake value of 2-[18F]FDG corrected for body weight (SUVBW). Results Abdominal SUVBW was significantly increased on day 1 (p < 0.0001), day 3 (p < 0.0001), and day 6 (p < 0.05) in the doxorubicin-treated group compared to controls. Abdominal SUVBW returned to baseline levels on day 10. In the doxorubicin group, the largest weight loss was observed on day 3 (control vs doxorubicin, mean percent of baseline weight: (98.5 ± 3.2% vs 87.9 ± 4.6%, p < 0.0001). Moreover, in the doxorubicin-treated group, villus lengths were decreased by 23-28% on days 1 and 3 in the small intestine (p < 0.05), and jejunal levels of tumour necrosis factor and interleukin-1β were significantly increased on day 3 (p < 0.05). Discussion Together, these findings indicate that sequential 2-[18F]FDG-PET/CT scans can objectively quantify and evaluate the development and resolution of intestinal inflammation over time in a mouse model of doxorubicin-induced mucositis.
Collapse
Affiliation(s)
- Sina Dalby
- Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Sofie Skallerup
- Department of Cancer and Inflammation Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Christina Baun
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
| | | | - Mathias Rathe
- Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Mikael Palner
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
| | - Steffen Husby
- Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jesper Bonnet Moeller
- Department of Cancer and Inflammation Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
- Danish Institute for Advanced Study, University of Southern Denmark, Odense, Denmark
| |
Collapse
|
|
11
|
Fooladi M, Shirazi A, Sheikhzadeh P, Amirrashedi M, Ghahramani F, Cheki M, Khoobi M. Investigating the attenuating effect of telmisartan against radiation-induced intestinal injury using 18F-FDG micro-PET imaging. Int J Radiat Biol 2022; 99:446-458. [PMID: 35930426 DOI: 10.1080/09553002.2022.2110295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
BACKGROUND AND OBJECTIVE This study was aimed to investigate the ability of 18F-Fluro-deoxy-glucose (18F-FDG)-based micro-positron emission tomography (microPET) imaging to evaluate the efficacy of telmisartan, a highly selective angiotensin II receptor antagonist (ARA), in intestinal tissue recovery process after in vivo irradiation. METHODS Male Balb/c mice were randomly divided into four groups of control, telmisartan, irradiation, and telmisartan + irradiation. A solution of telmisartan in phosphate-buffered saline (PBS) was administered orally at 12 mg/kg body weight for seven consecutive days prior to whole body exposing to a single sub-lethal dose of 5 Gy X-rays. The mice were imaged using 18F-FDG microPET at 9 and 30 days post-irradiation. The 18F-FDG uptake in jejunum was determined according to the mean standardized uptake value (SUVmean) index. Tissues were also processed in similar time points for histological analysis. RESULTS The 18F-FDG microPET imaging confirmed the efficacy of telmisartan as a potent attenuating agent for ionizing radiation-induced injury of intestine in mice model. The results were also in line with the histological analysis indicating that pretreatment with telmisartan reduced damage to the villi, crypts, and intestinal mucosa compared with irradiated and non-treated group from day 9 to 30 after irradiation. CONCLUSION The results revealed that 18F-FDG microPET imaging could be a good candidate to replace time-consuming and invasive biological techniques for screening of radioprotective agents. These findings were also confirmed by histological examinations which indicated that telmisartan can effectively attenuates radiation injury caused by ionizing-irradiation.
Collapse
Affiliation(s)
- Masoomeh Fooladi
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Shirazi
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Peyman Sheikhzadeh
- Department of Nuclear Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahsa Amirrashedi
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Ghahramani
- Radiotherapy-Oncology Center, Yas Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Cheki
- Department of Medical Imaging and Radiation Sciences, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mehdi Khoobi
- Biomaterials Group, Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
12
|
Schmoyer CJ, Saidman J, Bohl JL, Bierly CL, Kuemmerle JF, Bickston SJ. The Pathogenesis and Clinical Management of Stricturing Crohn Disease. Inflamm Bowel Dis 2021; 27:1839-1852. [PMID: 33693860 DOI: 10.1093/ibd/izab038] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Indexed: 02/07/2023]
Abstract
Stricturing of the gastrointestinal tract is a common complication in Crohn disease and is a significant cause of morbidity and mortality among this population. The inflammatory process initiates fibrosis, leading to aberrant wound healing and excess deposition of extracellular matrix proteins. Our understanding of this process has grown and encompasses cellular mechanisms, epigenetic modifications, and inherent genetic predisposition toward fibrosis. Although medications can improve inflammation, there is still no drug to attenuate scar formation. As such, management of stricturing disease requires a multidisciplinary and individualized approach including medical management, therapeutic endoscopy, and surgery. This review details the current understanding regarding the pathogenesis, detection, and management of stricturing Crohn disease.
Collapse
Affiliation(s)
- Christopher J Schmoyer
- Virginia Commonwealth University, Division of Gastroenterology and Hepatology, Richmond, Virginia, USA
| | - Jakob Saidman
- Virginia Commonwealth University, Division of Gastroenterology and Hepatology, Richmond, Virginia, USA
| | - Jaime L Bohl
- Virginia Commonwealth University, Division of Colorectal Surgery, Richmond, Virginia, USA
| | - Claire L Bierly
- Virginia Commonwealth University, Division of Gastroenterology and Hepatology, Richmond, Virginia, USA
| | - John F Kuemmerle
- Virginia Commonwealth University, Division of Gastroenterology and Hepatology, Richmond, Virginia, USA.,Virginia Commonwealth University, Department of Physiology and Biophysics, Richmond, Virginia, USA
| | - Stephen J Bickston
- Virginia Commonwealth University, Division of Gastroenterology and Hepatology, Richmond, Virginia, USA
| |
Collapse
|
|
13
|
Sepehrizadeh T, Jong I, DeVeer M, Malhotra A. PET/MRI in paediatric disease. Eur J Radiol 2021; 144:109987. [PMID: 34649143 DOI: 10.1016/j.ejrad.2021.109987] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 09/22/2021] [Accepted: 09/27/2021] [Indexed: 12/17/2022]
Abstract
Nuclear medicine and molecular imaging have a small but growing role in the management of paediatric and neonatal diseases. During the past decade, combined PET/MRI has emerged as a clinically important hybrid imaging modality in paediatric medicine due to diagnostic advantages and reduced radiation exposure compared to alternative techniques. The applications for nuclear medicine, radiopharmaceuticals and combined PET/MRI in paediatric diagnosis is broadly similar to adults, however there are some key differences. There are a variety of clinical applications for PET/MRI imaging in children including, but not limited to, oncology, neurology, cardiovascular, infection and chronic inflammatory diseases, and in renal-urological disorders. In this article, we review the applications of PET/MRI in paediatric and neonatal imaging, its current role, advantages and disadvantages over other hybrid imaging techniques such as PET/CT, and its future applications. Overall, PET/MRI is a powerful imaging technology in diagnostic medicine and paediatric diseases. Higher soft tissue contrasts and lower radiation dose of the MRI makes it the superior technology compared to other conventional techniques such as PET/CT or scintigraphy. However, this relatively new hybrid imaging has also some limitations. MRI based attenuation correction remains a challenge and although methodologies have improved significantly in the last decades, most remain under development.
Collapse
Affiliation(s)
| | - Ian Jong
- Department of diagnostic imaging, Monash Health, Melbourne, Australia
| | - Michael DeVeer
- Monash Biomedical Imaging, Monash University, Melbourne, Australia
| | - Atul Malhotra
- Monash Newborn, Monash Children's Hospital, Melbourne, Australia; Department of Paediatrics, Monash University, Melbourne, Australia
| |
Collapse
|
|
14
|
Tenhami M, Virtanen J, Kauhanen S, Koffert J, Kemppainen J, Saunavaara V, Kujari H, Hurme S, Teperi S, Voutilainen M. The value of combined positron emission tomography/magnetic resonance imaging to diagnose inflammatory bowel disease: a prospective study. Acta Radiol 2021; 62:851-857. [PMID: 32722966 DOI: 10.1177/0284185120944900] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND The clinical utility of positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison to standard work-up with patients with known or suspected inflammatory bowel disease (IBD) is unknown. PURPOSE To evaluate the value of 18F-fluorodeoxyglucose (18F-FDG) PET/MRI in the diagnostics of IBD and further compare the data obtained using PET/MRI to histological findings. MATERIALS AND METHODS Ten patients with relapse in IBD or with symptoms of suspected IBD were recruited either from a gastroenterology outpatient clinic or from a hospital ward. Intestinal inflammation was assessed with histology and 18F-FDG PET/MRI. Maximum standard uptake values (SUVmax) were calculated in six regions of the intestine (small bowel, ascending, transverse, descending and sigmoid colon, and rectum) and compared to histological analysis of inflammation activity. RESULTS The study showed that both the inflammation activity (P = 0.008) and the region of the biopsy in the intestine (P = 0.015) had a significant effect on SUV. SUVs obtained from severe inflammation activity emerged significantly from the background (P = 0.006). In addition, the SUVs obtained from moderate inflammation raised from background, but the difference was not statistically significant (P = 0.083), while SUVs of mild inflammation were at the same level with SUVs of normal bowel wall (P = 0.988). CONCLUSION 18F-FDG PET/MRI is a promising method of detecting especially severe inflammatory bowel lesions. More data are required to define its sensitivity and specificity.
Collapse
Affiliation(s)
- Mervi Tenhami
- Division of Digestive Surgery, Turku University Hospital, Turku, Finland
| | - Johanna Virtanen
- Department of Radiology, Turku University Hospital, Turku, Finland; Medical Imaging Centre of Southwest Finland, University of Turku, Turku, Finland
| | - Saila Kauhanen
- Division of Digestive Surgery, Turku University Hospital, Turku, Finland
| | - Jukka Koffert
- Department of Gastroenterology, Turku University Hospital, Turku, Finland
| | - Jukka Kemppainen
- Department of Clinical Physiology and Nuclear Medicine and Turku PET Centre, Turku University Hospital, Turku, Finland
| | - Virva Saunavaara
- Department of Medical Physics and Turku PET Centre, Turku University Hospital, Turku, Finland
| | - Harry Kujari
- Department of Pathology, Turku University Hospital, Turku, Finland
| | - Saija Hurme
- Department of Biostatistics, University of Turku, Turku, Finland
| | - Simo Teperi
- Department of Biostatistics, University of Turku, Turku, Finland
| | - Markku Voutilainen
- Department of Medicine, University of Turku, Turku, Finland
- Division of Medicine, Turku University Hospital, Turku, Finland
| |
Collapse
|
|
15
|
Gobert AP, Boutaud O, Asim M, Zagol-Ikapitte IA, Delgado AG, Latour YL, Finley JL, Singh K, Verriere TG, Allaman MM, Barry DP, McNamara KM, Sierra JC, Amarnath V, Tantawy MN, Bimczok D, Piazuelo MB, Washington MK, Zhao S, Coburn LA, Wilson KT. Dicarbonyl Electrophiles Mediate Inflammation-Induced Gastrointestinal Carcinogenesis. Gastroenterology 2021; 160:1256-1268.e9. [PMID: 33189701 PMCID: PMC7956217 DOI: 10.1053/j.gastro.2020.11.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 10/23/2020] [Accepted: 11/06/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Inflammation in the gastrointestinal tract may lead to the development of cancer. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid peroxidation during the inflammatory response and form covalent adducts with amine-containing macromolecules. Thus, we sought to determine the role of dicarbonyl electrophiles in inflammation-associated carcinogenesis. METHODS The formation of isoLG adducts was analyzed in the gastric tissues of patients infected with Helicobacter pylori from gastritis to precancerous intestinal metaplasia, in human gastric organoids, and in patients with colitis and colitis-associated carcinoma (CAC). The effect on cancer development of a potent scavenger of dicarbonyl electrophiles, 5-ethyl-2-hydroxybenzylamine (EtHOBA), was determined in transgenic FVB/N insulin-gastrin (INS-GAS) mice and Mongolian gerbils as models of H pylori-induced carcinogenesis and in C57BL/6 mice treated with azoxymethane-dextran sulfate sodium as a model of CAC. The effect of EtHOBA on mutations in gastric epithelial cells of H pylori-infected INS-GAS mice was assessed by whole-exome sequencing. RESULTS We show increased isoLG adducts in gastric epithelial cell nuclei in patients with gastritis and intestinal metaplasia and in human gastric organoids infected with H pylori. EtHOBA inhibited gastric carcinoma in infected INS-GAS mice and gerbils and attenuated isoLG adducts, DNA damage, and somatic mutation frequency. Additionally, isoLG adducts were elevated in tissues from patients with colitis, colitis-associated dysplasia, and CAC as well as in dysplastic tumors of C57BL/6 mice treated with azoxymethane-dextran sulfate sodium. In this model, EtHOBA significantly reduced adduct formation, tumorigenesis, and dysplasia severity. CONCLUSIONS Dicarbonyl electrophiles represent a link between inflammation and somatic genomic alterations and are thus key targets for cancer chemoprevention.
Collapse
Affiliation(s)
- Alain P Gobert
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee.
| | - Olivier Boutaud
- Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
| | - Mohammad Asim
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Irene A Zagol-Ikapitte
- Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Alberto G Delgado
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Yvonne L Latour
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jordan L Finley
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Kshipra Singh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Thomas G Verriere
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Margaret M Allaman
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Daniel P Barry
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Kara M McNamara
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Johanna C Sierra
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Venkataraman Amarnath
- Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Mohammed N Tantawy
- Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Diane Bimczok
- Department of Microbiology and Immunology, Montana State University, Bozeman, Montana
| | - M Blanca Piazuelo
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee
| | - M Kay Washington
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Shilin Zhao
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Lori A Coburn
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee
| | - Keith T Wilson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee
| |
Collapse
|
|
16
|
Casali M, Lauri C, Altini C, Bertagna F, Cassarino G, Cistaro A, Erba AP, Ferrari C, Mainolfi CG, Palucci A, Prandini N, Baldari S, Bartoli F, Bartolomei M, D’Antonio A, Dondi F, Gandolfo P, Giordano A, Laudicella R, Massollo M, Nieri A, Piccardo A, Vendramin L, Muratore F, Lavelli V, Albano D, Burroni L, Cuocolo A, Evangelista L, Lazzeri E, Quartuccio N, Rossi B, Rubini G, Sollini M, Versari A, Signore A. State of the art of 18F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation. Clin Transl Imaging 2021; 9:299-339. [PMID: 34277510 PMCID: PMC8271312 DOI: 10.1007/s40336-021-00445-w] [Citation(s) in RCA: 98] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 06/19/2021] [Indexed: 02/06/2023]
Abstract
AIM The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections. METHODS In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [18F]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020. RESULTS Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication. CONCLUSIONS Currently, [18F]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a "common nuclear physicians' language" throughout all the country. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s40336-021-00445-w.
Collapse
Affiliation(s)
- Massimiliano Casali
- Nuclear Medicine Unit, Azienda Unità Sanitaria Locale IRCCS, Reggio Emilia, Italy
| | - Chiara Lauri
- grid.7841.aNuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Corinna Altini
- grid.7644.10000 0001 0120 3326Nuclear Medicine Unit, Interdisciplinary Department of Medicine, University of Bari, Bari, Italy
| | - Francesco Bertagna
- grid.412725.7Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, Brescia, Italy
| | - Gianluca Cassarino
- grid.5608.b0000 0004 1757 3470Nuclear Medicine Unit, Department of Medicine DIMED, University of Padova, Padova, Italy
| | | | - Anna Paola Erba
- grid.5395.a0000 0004 1757 3729Regional Center of Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy
| | - Cristina Ferrari
- grid.7644.10000 0001 0120 3326Nuclear Medicine Unit, Interdisciplinary Department of Medicine, University of Bari, Bari, Italy
| | - Ciro Gabriele Mainolfi
- grid.4691.a0000 0001 0790 385XDepartment of Advanced Biomedical Sciences, University “Federico II”, Naples, Italy
| | - Andrea Palucci
- grid.415845.9Department of Nuclear Medicine, “Ospedali Riuniti di Torrette” Hospital, Ancona, Italy
| | - Napoleone Prandini
- grid.418324.80000 0004 1781 8749Nuclear Medicine Unit, Department of Diagnostic Imaging, Centro Diagnostico Italiano, Milan, Italy
| | - Sergio Baldari
- grid.10438.3e0000 0001 2178 8421Nuclear Medicine Unit, Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, University of Messina, Messina, Italy
| | - Francesco Bartoli
- grid.5395.a0000 0004 1757 3729Regional Center of Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy
| | - Mirco Bartolomei
- grid.416315.4Nuclear Medicine Unit, Oncological Medical and Specialists Department, University Hospital of Ferrara, Ferrara, Italy
| | - Adriana D’Antonio
- grid.4691.a0000 0001 0790 385XDepartment of Advanced Biomedical Sciences, University “Federico II”, Naples, Italy
| | - Francesco Dondi
- grid.412725.7Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, Brescia, Italy
| | - Patrizia Gandolfo
- grid.418324.80000 0004 1781 8749Nuclear Medicine Unit, Department of Diagnostic Imaging, Centro Diagnostico Italiano, Milan, Italy
| | - Alessia Giordano
- grid.4691.a0000 0001 0790 385XDepartment of Advanced Biomedical Sciences, University “Federico II”, Naples, Italy
| | - Riccardo Laudicella
- grid.10438.3e0000 0001 2178 8421Nuclear Medicine Unit, Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, University of Messina, Messina, Italy
| | | | - Alberto Nieri
- grid.416315.4Nuclear Medicine Unit, Oncological Medical and Specialists Department, University Hospital of Ferrara, Ferrara, Italy
| | | | - Laura Vendramin
- grid.5608.b0000 0004 1757 3470Nuclear Medicine Unit, Department of Medicine DIMED, University of Padova, Padova, Italy
| | - Francesco Muratore
- Rheumatology Unit, Azienda Unità Sanitaria Locale IRCCS, Reggio Emilia, Italy
| | - Valentina Lavelli
- grid.7644.10000 0001 0120 3326Nuclear Medicine Unit, Interdisciplinary Department of Medicine, University of Bari, Bari, Italy
| | - Domenico Albano
- grid.412725.7Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, Brescia, Italy
| | - Luca Burroni
- grid.415845.9Department of Nuclear Medicine, “Ospedali Riuniti di Torrette” Hospital, Ancona, Italy
| | - Alberto Cuocolo
- grid.4691.a0000 0001 0790 385XDepartment of Advanced Biomedical Sciences, University “Federico II”, Naples, Italy
| | - Laura Evangelista
- grid.5608.b0000 0004 1757 3470Nuclear Medicine Unit, Department of Medicine DIMED, University of Padova, Padova, Italy
| | - Elena Lazzeri
- grid.5395.a0000 0004 1757 3729Regional Center of Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy
| | - Natale Quartuccio
- grid.419995.9Nuclear Medicine Unit, A.R.N.A.S. Civico di Cristina and Benfratelli Hospitals, Palermo, Italy
| | - Brunella Rossi
- Nuclear Medicine Unit, Department of Services, ASUR MARCHE-AV5, Ascoli Piceno, Italy
| | - Giuseppe Rubini
- grid.7644.10000 0001 0120 3326Nuclear Medicine Unit, Interdisciplinary Department of Medicine, University of Bari, Bari, Italy
| | - Martina Sollini
- grid.417728.f0000 0004 1756 8807Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
| | - Annibale Versari
- Nuclear Medicine Unit, Azienda Unità Sanitaria Locale IRCCS, Reggio Emilia, Italy
| | - Alberto Signore
- grid.7841.aNuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, Rome, Italy
| |
Collapse
|
|
17
|
Seoane-Viaño I, Gómez-Lado N, Lázare-Iglesias H, García-Otero X, Antúnez-López JR, Ruibal Á, Varela-Correa JJ, Aguiar P, Basit AW, Otero-Espinar FJ, González-Barcia M, Goyanes A, Luzardo-Álvarez A, Fernández-Ferreiro A. 3D Printed Tacrolimus Rectal Formulations Ameliorate Colitis in an Experimental Animal Model of Inflammatory Bowel Disease. Biomedicines 2020; 8:E563. [PMID: 33276641 PMCID: PMC7761558 DOI: 10.3390/biomedicines8120563] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 11/24/2020] [Accepted: 11/27/2020] [Indexed: 12/11/2022] Open
Abstract
The aim of this study was to fabricate novel self-supporting tacrolimus suppositories using semisolid extrusion 3-dimensional printing (3DP) and to investigate their efficacy in an experimental model of inflammatory bowel disease. Blends of Gelucire 44/14 and coconut oil were employed as lipid excipients to obtain suppository formulations with self-emulsifying properties, which were then tested in a TNBS (2,4,6-trinitrobenzenesulfonic acid) induced rat colitis model. Disease activity was monitored using PET/CT medical imaging; maximum standardized uptake values (SUVmax), a measure of tissue radiotracer accumulation rate, together with body weight changes and histological assessments, were used as inflammatory indices to monitor treatment efficacy. Following tacrolimus treatment, a significant reduction in SUVmax was observed on days 7 and 10 in the rat colon sections compared to non-treated animals. Histological analysis using Nancy index confirmed disease remission. Moreover, statistical analysis showed a positive correlation (R2 = 71.48%) between SUVmax values and weight changes over time. Overall, this study demonstrates the effectiveness of 3D printed tacrolimus suppositories to ameliorate colitis and highlights the utility of non-invasive PET/CT imaging to evaluate new therapies in the preclinical area.
Collapse
Affiliation(s)
- Iria Seoane-Viaño
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain; (I.S.-V.); (X.G.-O.); (F.J.O.-E.)
- Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Noemí Gómez-Lado
- Nuclear Medicine Department and Molecular Imaging Group, University Clinical Hospital (CHUS) and Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (N.G.-L.); (Á.R.); (P.A.)
| | - Héctor Lázare-Iglesias
- Pathology Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), 15706 Santiago de Compostela, Spain; (H.L.-I.); (J.R.A.-L.)
| | - Xurxo García-Otero
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain; (I.S.-V.); (X.G.-O.); (F.J.O.-E.)
- Nuclear Medicine Department and Molecular Imaging Group, University Clinical Hospital (CHUS) and Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (N.G.-L.); (Á.R.); (P.A.)
| | - José Ramón Antúnez-López
- Pathology Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), 15706 Santiago de Compostela, Spain; (H.L.-I.); (J.R.A.-L.)
| | - Álvaro Ruibal
- Nuclear Medicine Department and Molecular Imaging Group, University Clinical Hospital (CHUS) and Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (N.G.-L.); (Á.R.); (P.A.)
- Tejerina Foundation, José Abascal 40, 28003 Madrid, Spain
| | - Juan Jesús Varela-Correa
- Pharmacy Department, University Hospital Ourense (SERGAS), Calle Ramón Puga Noguerol 54, 32005 Ourense, Spain;
| | - Pablo Aguiar
- Nuclear Medicine Department and Molecular Imaging Group, University Clinical Hospital (CHUS) and Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (N.G.-L.); (Á.R.); (P.A.)
| | - Abdul W. Basit
- FabRx Ltd., 3 Romney Road, Ashford, Kent TN24 0RW, UK;
- Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK
| | - Francisco J. Otero-Espinar
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain; (I.S.-V.); (X.G.-O.); (F.J.O.-E.)
- Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Miguel González-Barcia
- Pharmacy Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), 15706 Santiago de Compostela, Spain;
| | - Alvaro Goyanes
- FabRx Ltd., 3 Romney Road, Ashford, Kent TN24 0RW, UK;
- Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK
- Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma Group (GI-1645), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - Asteria Luzardo-Álvarez
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain; (I.S.-V.); (X.G.-O.); (F.J.O.-E.)
- Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Anxo Fernández-Ferreiro
- Pharmacy Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), 15706 Santiago de Compostela, Spain;
- Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| |
Collapse
|
|
18
|
Lee S, Kim SB, Lee J, Park J, Choi S, Hwang GS, Choi HS, Kang KS. Evaluation of Anti-Colitis Effect of KM1608 and Biodistribution of Dehydrocostus Lactone in Mice Using Bioimaging Analysis. PLANTS 2020; 9:plants9091175. [PMID: 32927852 PMCID: PMC7570101 DOI: 10.3390/plants9091175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/04/2020] [Accepted: 09/07/2020] [Indexed: 11/16/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing disorder modulated by numerous factors. Recent failures of drugs targeting single factors suggest that multitargeting drugs could be useful for the treatment of IBD. Natural medicines may be an alternative option for the treatment of IBD, owing to the complex nature of the disease. However, most natural medicines have poor in vitro and in vivo translational potential because of inadequate pharmacokinetic study. KM1608, a mixture of the medicinal plants Aucklandia lappa, Terminalia chebula, and Zingiber officinale, was examined for its anti-colitis effects and biodistribution using bioimaging. Dehydrocostus lactone, as a marker compound, was analyzed to assess the biodistribution of KM1608. KM1608 significantly attenuated the disease activity of dextran sodium sulfate-induced colitis in mice and suppressed inflammatory mediators such as myeloperoxidase, proinflammatory cytokines (TNF-α and IL-6), and the Th2-type cytokine IL-4 in the colon. Optical fluorescence imaging revealed that KM1608 was distributed in the intestinal area as a target organ. Collectively, our findings suggest that KM1608 is a potential therapeutic formulation for IBD.
Collapse
Affiliation(s)
- Sullim Lee
- College of Bio-Nano Technology, Gachon University, Seongnam-si, Gyeonggi-do 13120, Korea;
| | - Sang-Back Kim
- Kolmar Korea R&D Complex, Kolmar, Korea Co. Ltd, 61, Heolleung-ro 8-gil, Seocho-gu, Seoul 06500, Korea; (S.-B.K.); (J.P.)
| | - Jaemin Lee
- College of Korean Medicine, Gachon University, Seongnam-si, Gyeonggi-do 13120, Korea; (J.L.); (S.C.); (G.S.H.)
| | - Jimin Park
- Kolmar Korea R&D Complex, Kolmar, Korea Co. Ltd, 61, Heolleung-ro 8-gil, Seocho-gu, Seoul 06500, Korea; (S.-B.K.); (J.P.)
| | - Sungyoul Choi
- College of Korean Medicine, Gachon University, Seongnam-si, Gyeonggi-do 13120, Korea; (J.L.); (S.C.); (G.S.H.)
| | - Gwi Seo Hwang
- College of Korean Medicine, Gachon University, Seongnam-si, Gyeonggi-do 13120, Korea; (J.L.); (S.C.); (G.S.H.)
| | - Han-Seok Choi
- Kolmar Korea R&D Complex, Kolmar, Korea Co. Ltd, 61, Heolleung-ro 8-gil, Seocho-gu, Seoul 06500, Korea; (S.-B.K.); (J.P.)
- Correspondence: (H.-S.C.); (K.S.K.); Tel.: +82-2-3459-5753 (H.-S.C.); +82-31-750-5402 (K.S.K.)
| | - Ki Sung Kang
- College of Korean Medicine, Gachon University, Seongnam-si, Gyeonggi-do 13120, Korea; (J.L.); (S.C.); (G.S.H.)
- Correspondence: (H.-S.C.); (K.S.K.); Tel.: +82-2-3459-5753 (H.-S.C.); +82-31-750-5402 (K.S.K.)
| |
Collapse
|
|
19
|
Li Y, Khamou M, Schaarschmidt BM, Umutlu L, Forsting M, Demircioglu A, Haubold J, Koch AK, Bruckmann NM, Sawicki LM, Herrmann K, Boone JH, Langhorst J. Comparison of 18F-FDG PET-MR and fecal biomarkers in the assessment of disease activity in patients with ulcerative colitis. Br J Radiol 2020; 93:20200167. [PMID: 32579403 DOI: 10.1259/bjr.20200167] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
OBJECTIVE To compare the diagnostic performance of fecal biomarkers and 18F-fludeoxyglucose (18F-FDG) positron emmision tomography-MR (PET-MR) in the assessment of disease activity in patients with ulcerative colitis. METHODS This study was conducted under the framework of a single-center clinical trial (clinicaltrials.gov [NCT03781284]). N = 50 participants were enrolled. Fecal samples were collected before bowel preparation. All patients underwent whole-body 18F-FDG PET-MR followed by ileocolonoscopy within 24 h. Diagnostic performance of five fecal biomarkers (calprotectin, lactoferrin, polymorphonuclear leukocyte elastase, S100A12 and eosinophil-derived neurotoxin), MR morphological parameters (MRmorph), diffusion-weighted imaging and PET in detecting active disease determined by Rachmilewitz endoscopic activity index (EAI) were evaluated and compared with each other. Correlations between fecal biomarkers, PET and endoscopy were calculated. RESULTS According to EAI, n = 38 patients presented with endoscopically active disease (16 mild, 19 moderate and 3 severe). All five biomarkers, PET and MRmorph could differentiate endoscopically active disease from endoscopic remission without significant difference regarding their operating characteristics (accuracies between 0.673 for calprotectin and 0.898 for lactoferrin). In predicting endoscopically moderate to severe disease, PET showed the highest diagnostic performance (accuracy = 0.857) compared to calprotectin and lactoferrin (accuracy = 0.633 and 0.735). PET had also the strongest correlation with endoscopy (ρ = 0.685, p < 0.001), while within fecal biomarkers the levels of lactoferrin and eosinophil-derived neurotoxin correlated significantly with EAI (ρ = 0.423 and 0.528, both p < 0.05). CONCLUSION Both fecal biomarkers and PET-MR were excellent non-invasive diagnostic tools in the assessment of disease activity in ulcerative colitis. ADVANCES IN KNOWLEDGE Both fecal biomarkers and PET-MR parameters are able to predict endoscopically active disease with comparable diagnostic performance. PET had the highest correlation with endoscopy and outperformed fecal biomarkers in differentiating moderate to severe from mild disease.
Collapse
Affiliation(s)
- Yan Li
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Michael Khamou
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Benedikt Michael Schaarschmidt
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Lale Umutlu
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Michael Forsting
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Aydin Demircioglu
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Johannes Haubold
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Anna Katharina Koch
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Am Deimelsberg 34a, 45276 Essen, Germany
| | - Nils-Martin Bruckmann
- Department of Diagnostic and Interventional Radiology, University Hospital Dusseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany
| | - Lino Morris Sawicki
- Department of Diagnostic and Interventional Radiology, University Hospital Dusseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany
| | - Ken Herrmann
- Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - James Hunter Boone
- Research and Development, TechLab, INC., 2001 Kraft Drive, Blacksburg, USA
| | - Jost Langhorst
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Am Deimelsberg 34a, 45276 Essen, Germany.,Department for Internal and Integrative Medicine, Social Foundation Bamberg, Clinic Bamberg, Buger Straße 80, 96049 Bamberg, Germany.,Chair for Integrative Medicine, University of Duisburg-Essen, Am Deimelsberg 34a, 45276 Essen, Germany
| |
Collapse
|
|
20
|
Kim DH, Chang KJ, Fowler KJ, Cash BD, Garcia EM, Kambadakone AR, Levy AD, Liu PS, Mace SE, Marin D, Moreno C, Peterson CM, Pietryga JA, Solnes LB, Weinstein S, Carucci LR. ACR Appropriateness Criteria® Crohn Disease. J Am Coll Radiol 2020; 17:S81-S99. [PMID: 32370980 DOI: 10.1016/j.jacr.2020.01.030] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 01/22/2020] [Indexed: 02/08/2023]
Abstract
Three common clinical scenarios involving use of imaging in Crohn disease are covered. These include the initial evaluation of Crohn disease when the diagnosis has not been previously established, the evaluation for anticipated exacerbation of known disease, and the evaluation of disease activity during therapy monitoring. The appropriateness of a given imaging modality for each scenario is rated as one of three categories (usually appropriate, may be appropriate, usually not appropriate) to help guide evaluation. Pediatric presentation of Crohn disease and the appropriateness of imaging are not covered in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Collapse
Affiliation(s)
- David H Kim
- Panel Chair, University of Wisconsin Hospital & Clinics, Madison, Wisconsin.
| | | | - Kathryn J Fowler
- Panel Vice-Chair, University of California San Diego, San Diego, California
| | - Brooks D Cash
- University of Texas Health Science Center at Houston and McGovern Medical School, Houston, Texas; American Gastroenterological Association
| | - Evelyn M Garcia
- Virginia Tech Carilion School of Medicine, Roanoke, Virginia
| | | | - Angela D Levy
- Medstar Georgetown University Hospital, Washington, District of Columbia
| | | | - Sharon E Mace
- Cleveland Clinic, Cleveland, Ohio; American College of Emergency Physicians
| | - Daniele Marin
- Duke University Medical Center, Durham, North Carolina
| | | | | | | | | | | | - Laura R Carucci
- Specialty Chair, Virginia Commonwealth University Medical Center, Richmond, Virginia
| |
Collapse
|
|
21
|
Frickenstein AN, Jones MA, Behkam B, McNally LR. Imaging Inflammation and Infection in the Gastrointestinal Tract. Int J Mol Sci 2019; 21:ijms21010243. [PMID: 31905812 PMCID: PMC6981656 DOI: 10.3390/ijms21010243] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 12/23/2019] [Accepted: 12/25/2019] [Indexed: 02/06/2023] Open
Abstract
A variety of seemingly non-specific symptoms manifest within the gastrointestinal (GI) tract, particularly in the colon, in response to inflammation, infection, or a combination thereof. Differentiation between symptom sources can often be achieved using various radiologic studies. Although it is not possible to provide a comprehensive survey of imaging gastrointestinal GI tract infections in a single article, the purpose of this review is to survey several topics on imaging of GI tract inflammation and infections. The review discusses such modalities as computed tomography, positron emission tomography, ultrasound, endoscopy, and magnetic resonance imaging while looking at up-an-coming technologies that could improve diagnoses and patient comfort. The discussion is accomplished through examining a combination of organ-based and organism-based approaches, with accompanying selected case examples. Specific focus is placed on the bacterial infections caused by Shigella spp., Escherichia coli, Clostridium difficile, Salmonella, and inflammatory conditions of diverticulitis and irritable bowel disease. These infectious and inflammatory diseases and their detection via molecular imaging will be compared including the appropriate differential diagnostic considerations.
Collapse
Affiliation(s)
- Alex N. Frickenstein
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (A.N.F.); (M.A.J.)
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA
| | - Meredith A. Jones
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (A.N.F.); (M.A.J.)
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA
| | - Bahareh Behkam
- Department of Mechanical Engineering, Virginia Tech University, Blacksburg, VA 24061, USA;
| | - Lacey R. McNally
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (A.N.F.); (M.A.J.)
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA
- Department of Surgery, University of Oklahoma, Oklahoma City, OK 73104, USA
- Correspondence:
| |
Collapse
|
|
22
|
Li Y, Schaarschmidt B, Umutlu L, Forsting M, Demircioglu A, Koch AK, Martin O, Herrmann K, Juette H, Tannapfel A, Langhorst J. 18F-FDG PET-MR enterography in predicting histological active disease using the Nancy index in ulcerative colitis: a randomized controlled trial. Eur J Nucl Med Mol Imaging 2019; 47:768-777. [DOI: 10.1007/s00259-019-04535-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 09/12/2019] [Indexed: 01/17/2023]
|
|
23
|
Chen W, Shen B, Sun X. Analysis of Progress and Challenges of EGFR-Targeted Molecular Imaging in Cancer With a Focus on Affibody Molecules. Mol Imaging 2019; 18:1536012118823473. [PMID: 30799684 PMCID: PMC6348515 DOI: 10.1177/1536012118823473] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Epidermal growth factor receptor (EGFR)-targeted cancer therapy requires an accurate estimation of EGFR expression in tumors to identify responsive patients, monitor therapeutic effect, and estimate prognosis. The EGFR molecular imaging is an optimal method for evaluating EGFR expression in vivo accurately and noninvasively. In this review, we discuss the recent advances in EGFR-targeted molecular imaging in cancer, with a special focus on the development of imaging agents, including epidermal growth factor (EGF) ligand, monoclonal antibodies, antibody fragments, Affibody, and small molecules. Each substrate or probe, whether it is an endogenous ligand, antibody, peptide, or small molecule labeled with fluorochrome or radionuclide, has unique advantages and limitations. Antibody-based probes have high affinity but a long metabolic cycle and therefore offer poor imaging quality. Affibody molecules promise to surpass antibody-based probes due to their small size, stable chemical properties, and high affinity to the target. Small-molecule probes are safe, have favorable pharmacokinetics, and show high affinity and specificity, in addition to having an ideal size, but are inadequate for delayed imaging after injection due to their fast clearance.
Collapse
Affiliation(s)
- Weizhi Chen
- 1 Molecular Imaging Research Center, Harbin Medical University, Heilongjiang, China.,2 TOF-PET/CT/MR Center, The Fourth Hospital of Harbin Medical University, Heilongjiang, China
| | - Baozhong Shen
- 1 Molecular Imaging Research Center, Harbin Medical University, Heilongjiang, China.,2 TOF-PET/CT/MR Center, The Fourth Hospital of Harbin Medical University, Heilongjiang, China
| | - Xilin Sun
- 1 Molecular Imaging Research Center, Harbin Medical University, Heilongjiang, China.,2 TOF-PET/CT/MR Center, The Fourth Hospital of Harbin Medical University, Heilongjiang, China
| |
Collapse
|
|
24
|
Cussó L, Desco M. Suppression of 18F-FDG signal in the bladder on small animal PET-CT. PLoS One 2018; 13:e0205610. [PMID: 30332442 PMCID: PMC6192599 DOI: 10.1371/journal.pone.0205610] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 09/27/2018] [Indexed: 11/17/2022] Open
Abstract
Introduction Retention of 2-deoxy-2-[18F]fluoro-D-glucose 18F-FDG in the bladder causes more problems in small animal research than in human research owing to the smaller size of the subject. Catheterization has been proposed to reduce bladder spillover both in human studies and in small animal research. Noninvasive alternatives such as hydration plus furosemide also seem to be a promising pre-imaging strategy for decreasing bladder spillover. Our main goal was to measure the effects of the combination of furosemide and hydration for reducing bladder signal directly on mouse bowel 18F-FDG-PET images. Methods Nine mice were divided into two groups: the control group (C, n = 4) and the treatment group (n = 5). The clearance protocol combines hyperhydration and a single furosemide dose during the 18F-FDG uptake period. Two images were acquired on different days in treated mice to evaluate two different furosemide doses (low dose, LD, 3.5 mg/kg; and high dose, HD, 7 mg/kg). A region of interest was drawn on each computed tomography image (bladder, kidneys, liver, muscle, and bone marrow). To quantify bladder spillover, two different areas of the colon were selected. Results A remarkable reduction in bladder spillover was achieved on 18F-FDG -PET in both groups. Our imaging findings were quantified, and both furosemide doses induced a decrease in mean standard uptake values (SUVmean) compared with the controls (LD 1.46 ± 0.54 and HD 1.05 ± 0.29; controls: 8.90 ± 3.4 [p-value < 0.05]). Conclusion We validated a non-invasive, easy, and harmless pre-imaging alternative for decreasing 18F-FDG bladder spillover. Our study shows the effect of furosemide on bladder spillover directly on 18F-FDG-PET images by measuring SUVmean in the bladder, colon, liver, muscle, and bone marrow.
Collapse
Affiliation(s)
- Lorena Cussó
- Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.,Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.,Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain
| | - Manuel Desco
- Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.,Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.,Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain
| |
Collapse
|
|
25
|
Catalano O, Kilcoyne A, Signore A, Mahmood U, Rosen B. Lower Gastrointestinal Tract Applications of PET/Computed Tomography and PET/MR Imaging. Radiol Clin North Am 2018; 56:821-834. [PMID: 30119776 DOI: 10.1016/j.rcl.2018.05.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This article discusses the role of PET/CT and PET/MR imaging in the evaluation of inflammatory and malignant disorders of the lower gastrointestinal tract. This includes a review of the current literature and a discussion of new and emerging research.
Collapse
|
|
26
|
Freise AC, Zettlitz KA, Salazar FB, Tavaré R, Tsai WTK, Chatziioannou AF, Rozengurt N, Braun J, Wu AM. Immuno-PET in Inflammatory Bowel Disease: Imaging CD4-Positive T Cells in a Murine Model of Colitis. J Nucl Med 2018; 59:980-985. [PMID: 29326360 DOI: 10.2967/jnumed.117.199075] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 12/24/2017] [Indexed: 12/22/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) in humans are characterized in part by aberrant CD4-positive (CD4+) T-cell responses. Currently, identification of foci of inflammation within the gut requires invasive procedures such as colonoscopy and biopsy. Molecular imaging with antibody fragment probes could be used to noninvasively monitor cell subsets causing intestinal inflammation. Here, GK1.5 cys-diabody (cDb), an antimouse CD4 antibody fragment derived from the GK1.5 hybridoma, was used as a PET probe for CD4+ T cells in the dextran sulfate sodium (DSS) mouse model of IBD. Methods: The DSS mouse model of IBD was validated by assessing changes in CD4+ T cells in the spleen and mesenteric lymph nodes (MLNs) using flow cytometry. Furthermore, CD4+ T cell infiltration in the colons of colitic mice was evaluated using immunohistochemistry. 89Zr-labeled GK1.5 cDb was used to image distribution of CD4+ T cells in the abdominal region and lymphoid organs of mice with DSS-induced colitis. Region-of-interest analysis was performed on specific regions of the gut to quantify probe uptake. Colons, ceca, and MLNs were removed and imaged ex vivo by PET. Imaging results were confirmed by ex vivo biodistribution analysis. Results: An increased number of CD4+ T cells in the colons of colitic mice was confirmed by anti-CD4 immunohistochemistry. Increased uptake of 89Zr-maleimide-deferoxamine (malDFO)-GK1.5 cDb in the distal colon of colitic mice was visible in vivo in PET scans, and region-of-interest analysis of the distal colon confirmed increased activity in DSS mice. MLNs from colitic mice were enlarged and visible in PET images. Ex vivo scans and biodistribution confirmed higher uptake in DSS-treated colons (DSS, 1.8 ± 0.40; control, 0.45 ± 0.12 percentage injected dose [%ID] per organ, respectively), ceca (DSS, 1.1 ± 0.38; control, 0.35 ± 0.09 %ID per organ), and MLNs (DSS, 1.1 ± 0.58; control, 0.37 ± 0.25 %ID per organ). Conclusion:89Zr-malDFO-GK1.5 cDb detected CD4+ T cells in the colons, ceca, and MLNs of colitic mice and may prove useful for further investigations of CD4+ T cells in preclinical models of IBD, with potential to guide development of antibody-based imaging in human IBD.
Collapse
Affiliation(s)
- Amanda C Freise
- Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California; and
| | - Kirstin A Zettlitz
- Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California; and
| | - Felix B Salazar
- Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California; and
| | - Richard Tavaré
- Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California; and
| | - Wen-Ting K Tsai
- Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California; and
| | - Arion F Chatziioannou
- Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California; and
| | - Nora Rozengurt
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Jonathan Braun
- Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California; and.,Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Anna M Wu
- Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California; and
| |
Collapse
|
|
27
|
Palatka K, Kacska S, Lovas S, Garai I, Varga J, Galuska L. The potential role of FDG PET-CT in the characterization of the activity of Crohn's disease, staging follow-up and prognosis estimation: a pilot study. Scand J Gastroenterol 2018; 53:24-30. [PMID: 29043862 DOI: 10.1080/00365521.2017.1390600] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES FDG PET-CT is a global, noninvasive, sensitive method to determine the location and activity of inflammatory lesions. Segmental FDG uptake is proportional with immune cell infiltration of bowel. Our aim was to evaluate prospectively the role of PET in patients with active Crohn's disease (CD) before and after one year's biological therapy, and to compare simple endoscopic score for CD (SES-CD), CD activity index (CDAI) and global PET scores. We also analyzed the prognostic value of initial PET scores. PATIENTS Twelve patients were selected: six male/six female, ages between 18 and 39, average: 24 years, with CDAI values >300. METHODS We scored the FDG uptake in the small intestine and the four colon segments (on a scale 0-3 for each), and summed them thus forming a global PET score. The scoring was based on the maximal standardized uptake value of the intestinal segment, related to the SUVmax of the liver (as a reference for normal tissue activity). The SES-CD, CDAI and global PET scores before and after treatment were statistically compared. RESULTS There were significant changes in CDAI and SES-CD after therapy, PET scores improved only in patients' subgroup with high (>4) initial PET score, indicating good prognosis of biological treatment. In active disease, PET was more informative than endoscopy to access the extent of the inflammation, and small intestine involvement. CONCLUSIONS FDG PET-CT score is a promising, noninvasive complementary method in the staging, treatment planning and follow-up of CD. Limitation of the study is the small number of patients.
Collapse
Affiliation(s)
- Károly Palatka
- a Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
| | - Sándor Kacska
- a Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
| | - Szilvia Lovas
- a Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
| | | | - József Varga
- c Department of Medical Imaging, Division of Nuclear Medicine, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
| | - László Galuska
- c Department of Medical Imaging, Division of Nuclear Medicine, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
| |
Collapse
|
|
28
|
Catalano OA, Kilcoyne A, Lauri C, Signore A. PET/MRI in Inflammatory Diseases. PET/MR IMAGING: CURRENT AND EMERGING APPLICATIONS 2018:123-135. [DOI: 10.1007/978-3-319-69641-6_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
29
|
Nowacki TM, Bettenworth D, Brückner M, Cordes F, Lenze F, Becker A, Wildgruber M, Eisenblätter M. Fluorescence-mediated Tomography for the Detection and Quantification of Macrophage-related Murine Intestinal Inflammation. J Vis Exp 2017. [PMID: 29286467 DOI: 10.3791/55942] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Murine models of disease are indispensable to scientific research. However, many diagnostic tools such as endoscopy or tomographic imaging are not routinely employed in animal models. Conventional experimental readouts often rely on post mortem and ex vivo analyses, which prevent intra-individual follow-up examinations and increase the number of study animals needed. Fluorescence-mediated tomography enables the non-invasive, repetitive, quantitative, three-dimensional assessment of fluorescent probes. It is highly sensitive and permits the use of molecular makers, which allows for the specific detection and characterization of distinct molecular targets. In particular, targeted probes represent an innovative tool for analyzing gene activation and protein expression in inflammation, autoimmune disease, infection, vascular disease, cell migration, tumorigenesis, etc. In this article, we provide step-by-step instructions on this sophisticated imaging technology for the in vivo detection and characterization of inflammation (i.e., F4/80-positive macrophage infiltration) in a widely used murine model of intestinal inflammation. This technique might also be used in other research areas, such as immune cell or stem cell tracking.
Collapse
Affiliation(s)
| | | | | | | | - Frank Lenze
- Department of Medicine B, University Hospital Münster
| | - Anne Becker
- Translational Research Imaging Center, Department of Clinical Radiology, University Hospital Münster
| | - Moritz Wildgruber
- Translational Research Imaging Center, Department of Clinical Radiology, University Hospital Münster
| | - Michel Eisenblätter
- Translational Research Imaging Center, Department of Clinical Radiology, University Hospital Münster
| |
Collapse
|
|
30
|
Evaluating [ 11C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis. Mol Imaging Biol 2017; 19:68-76. [PMID: 27402092 PMCID: PMC5209392 DOI: 10.1007/s11307-016-0979-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Purpose Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that affects an increasing number of patients. High comorbidity is observed between UC and other diseases in which inflammation may be involved, including brain diseases such as cognitive impairment, mental disorders, anxiety, and depression. To investigate the increased occurrence of these brain diseases in patients with UC, non-invasive methods for monitoring peripheral and central inflammation could be applied. Therefore, the goal of this study is to assess the feasibility of monitoring gut and brain inflammation in a rat model of chemically induced colitis by positron emission tomography (PET) with [11C]PBR28, a tracer targeting the translocator protein (TSPO), which is upregulated when microglia and macrophages are activated. Procedures Colitis was induced in rats by intra-rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Rats with colitis and healthy control animals were subjected to [11C]PBR28 PET of the abdomen followed by ex vivo biodistribution in order to assess whether inflammation in the gut could be detected. Another group of rats with colitis underwent repetitive [11C]PBR28 PET imaging of the brain to investigate the development of neuroinflammation. Results Eleven days after TNBS injection, ex vivo biodistribution studies demonstrated increased [11C]PBR28 uptake in the inflamed cecum and colon of rats with colitis as compared to healthy controls, whereas PET imaging did not show any difference between groups at any time. Similarly, repetitive PET imaging of the brain did not reveal any neuroinflammation induced by the TNBS administration in the colon. In contrast, significantly increased [11C]PBR28 uptake in cerebellum could be detected in ex vivo biodistribution studies on day 11. Conclusion Inflammation in both the gut and the brain of rats with chemically induced colitis was observed by ex vivo biodistribution. However, these effects could not be detected by [11C]PBR28 PET imaging in our colitis model, which is likely due to spill-over effects and insufficient resolution of the PET camera.
Collapse
|
|
31
|
TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases? CONTRAST MEDIA & MOLECULAR IMAGING 2017; 2017:6592139. [PMID: 29114179 PMCID: PMC5632884 DOI: 10.1155/2017/6592139] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Revised: 08/01/2017] [Accepted: 08/07/2017] [Indexed: 02/07/2023]
Abstract
Peripheral sterile inflammatory diseases (PSIDs) are a heterogeneous group of disorders that gathers several chronic insults involving the cardiovascular, respiratory, gastrointestinal, or musculoskeletal system and wherein inflammation is the cornerstone of the pathophysiology. In PSID, timely characterization and localization of inflammatory foci are crucial for an adequate care for patients. In brain diseases, in vivo positron emission tomography (PET) exploration of inflammation has matured over the last 20 years, through the development of radiopharmaceuticals targeting the translocator protein-18 kDa (TSPO) as molecular biomarkers of activated microglia. Recently, TSPO has been introduced as a possible molecular target for PSIDs PET imaging, making this protein a potential biomarker to address disease heterogeneity, to assist in patient stratification, and to contribute to predicting treatment response. In this review, we summarized the major research advances recently made in the field of TSPO PET imaging in PSIDs. Promising preliminary results have been reported in bowel, cardiovascular, and rheumatic inflammatory diseases, consolidated by preclinical studies. Limitations of TSPO PET imaging in PSIDs, regarding both its large expression in healthy peripheral tissues, unlike in central nervous system, and the production of peripheral radiolabeled metabolites, are also discussed, regarding their possible consequences on TSPO PET signal's quantification.
Collapse
|
|
32
|
|
|
33
|
Treglia G, Sadeghi R, Viccaro A, Muoio B, Giovanella L. Clinical role and accuracy of 18F-FDG PET in evaluating disease activity in patients with chronic inflammatory bowel disease: an updated systematic review and a bivariate meta-analysis. Clin Transl Imaging 2017. [DOI: 10.1007/s40336-017-0234-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
|
|
34
|
Signore A, Glaudemans AWJM, Gheysens O, Lauri C, Catalano OA. Nuclear Medicine Imaging in Pediatric Infection or Chronic Inflammatory Diseases. Semin Nucl Med 2017; 47:286-303. [PMID: 28417857 DOI: 10.1053/j.semnuclmed.2016.12.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
In this review article, we focus on the most recent applications of nuclear medicine techniques (mainly 99mTc/111In white blood cells (WBC) scan, [18F]-FDG-PET/CT, [18F]-FDG-PET/MRI, and 99mTc-IL-2 scintigraphy) in the study of children affected by peripheral bone osteomyelitis, fungal infections, inflammatory bowel diseases, and type 1 diabetes, owing to recent important published evidences of their role in the management of these diseases. For osteomyelitis in children, both bone scintigraphy and [18F]-FDG-PET have a major advantage of assessing the whole body in one imaging session to confirm or exclude multifocal involvement, whereas WBC scan has a limited role. In children with fungal infections, [18F]-FDG-PET can help in defining the best location for biopsy and can help in evaluating the extent of the infection and organs involved (also sites that were not yet clinically apparent), although its main role is for therapy monitoring. In inflammatory bowel diseases, and Crohn disease in particular, WBC scan has been successfully used for many years, but it is now used only in case of doubtful magnetic resonance (MR) or when MR cannot be performed and endoscopy is inconclusive. By contrast, there is an accumulating evidence of the role of [18F]-FDG-PET in management of children with Crohn disease, and PET/MR could be a versatile and innovative hybrid imaging technique that combines the metabolic information of PET with the high soft tissue resolution of MR, particularly for distinguishing fibrotic from active strictures. Finally, there are several new radiopharmaceuticals that specifically target inflammatory cells involved in the pathogenesis of insulitis aiming at developing new specific immunotherapies and to select children candidates to these treatments for improving their quality of life.
Collapse
Affiliation(s)
- Alberto Signore
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and Translational Medicine, "Sapienza" University of Rome, Rome, Italy.
| | - Andor W J M Glaudemans
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Olivier Gheysens
- Department of Nuclear Medicine and Molecular imaging, University Hospitals Leuven, Leuven, Belgium
| | - Chiara Lauri
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and Translational Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Onofrio A Catalano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| |
Collapse
|
|
35
|
Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohn's Disease. Inflamm Bowel Dis 2016; 22:2619-2629. [PMID: 27753695 DOI: 10.1097/mib.0000000000000924] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Fluorine-fluorodeoxyglucose positron emission tomography (F-FDG PET) has recently attracted interest for the measurement of disease activity in Crohn's disease (CD). The aim of this study was to assess the utility of FDG-PET as a marker of progression of inflammatory activity and its response to treatment in patients with CD. METHODS Twenty-two patients with active CD were recruited prospectively to undergo FDG-PET scanning at 2 time points. All 22 index scans were used to assess sensitivity and specificity against a reference standard magnetic resonance imaging measure. Correlations with clinicopathological markers of severity (Harvey-Bradshaw Index, C-reactive protein, and calprotectin) were also performed. Of note, 17/22 patients participated in the longitudinal component and underwent scanning before and 12 weeks after the initiation of anti-tumor necrosis factor alpha therapy. Patients were subcategorized on the basis of a clinically significant response, and responsiveness of the PET measures was assessed using previously described indices. Of note, 5/22 patients took part in the test-retest component of the study and underwent scanning twice within a target interval of 1 week, to assess the reproducibility of the PET measures. RESULTS The sensitivity and specificity of F-FDG PET were 88% and 70%, respectively. Standardized uptake value (SUV)-related PET measures correlated significantly both with C-reactive protein and Harvey-Bradshaw Index in cross-sectional and longitudinal analyses. (G)SUVMAX and (G)SUVMEAN demonstrated favorable responsiveness and reliability characteristics (responsiveness ratio of Guyatt >0.80 and % variability <20%) compared with volume-dependent FDG-PET measures. A proportion of the FDG signal (10%-30%) was found to originate from the lumen of diseased segments. CONCLUSIONS F-FDG PET may be useful for longitudinal monitoring of inflammatory activity in CD.
Collapse
|
|
36
|
Kaaru E, Bianchi A, Wunder A, Rasche V, Stiller D. Molecular Imaging in Preclinical Models of IBD with Nuclear Imaging Techniques: State-of-the-Art and Perspectives. Inflamm Bowel Dis 2016; 22:2491-8. [PMID: 27580387 DOI: 10.1097/mib.0000000000000904] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is characterized by chronic unregulated inflammation of the intestinal mucosa of the gastrointestinal tract. To date, this pathology has no cure. Colonoscopy and biopsies are the current gold standard diagnostic tools. However, being a chronic disease, IBD requires continuous follow-up to check for disease progress, treatment response, and remission. Unfortunately, these 2 diagnostic procedures are invasive and generally unable to show the cellular and molecular changes that take place in vivo. In this context, it is clear that there is a strong need for optimized noninvasive imaging techniques able to overcome the aforementioned limitations. This review aims to bring to light the scientific advancements that have been achieved so far in nuclear medicine in relation to tracking of immune cells involved in the preclinical models of IBD. In particular, this review will explore the advantages and limitations of the radiopharmaceuticals that aim to track whole cells like neutrophils, those that involve the radiolabeling of immune cell substrates or available human IBD medical therapies, and those that aim to track cell signaling molecules (e.g., cytokines and cell adhesion molecules). After a detailed critical summary of the state-of-the art, the challenges and perspectives of molecular imaging applied to IBD studies will be analyzed. Special attention will be paid to the translational potential of the described techniques and on the potential impact of these innovative approaches on the drug discovery pipelines and their contribution to the evolution of personalized medicine.
Collapse
Affiliation(s)
- Eric Kaaru
- *Target Discovery Research Department, In-Vivo Imaging Laboratory, Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach an der Riss, Germany; †Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach an der Riss, Germany; ‡Core Facility Small Animal Imaging, Ulm University, Ulm, Germany; and §Internal Medicine II, University Hospital Ulm, Ulm, Germany
| | | | | | | | | |
Collapse
|
|
37
|
Pellino G, Nicolai E, Catalano OA, Campione S, D'Armiento FP, Salvatore M, Cuocolo A, Selvaggi F. PET/MR Versus PET/CT Imaging: Impact on the Clinical Management of Small-Bowel Crohn's Disease. J Crohns Colitis 2016; 10:277-85. [PMID: 26574490 PMCID: PMC4957472 DOI: 10.1093/ecco-jcc/jjv207] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 11/03/2015] [Accepted: 11/06/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS The aim of this study was to compare the accuracy and clinical impact of hybrid positron emission tomography [PET]/magnetic resonance-enterography [MR-E] and PET/computed tomography-enterography [CT-E] in patients with Crohn's disease [CD]. METHODS A total of 35 patients with symptomatic small-bowel CD who were scheduled to undergo operation were evaluated before operation by same-day PET/CT-E and PET/MR-E. PET/MR-E was also compared with MR-E alone. Imaging accuracy for detecting pathological sites and discriminating between fibrotic and inflammatory strictures was assessed. Treatment was adjusted according to imaging findings and change in medical/surgical strategy was also evaluated. RESULTS PET/CT-E, PET/MR-E, and MR-E were equally accurate in detecting CD sites. PET/MR-E was more accurate in assessing extra-luminal disease [p = 0.002], which was associated with higher need for stoma [p = 0.022] and distant localisation [p = 0.002]. When the latter was observed, laparoscopy was started with hand-assisted device, reducing operative time [p = 0.022]. PET/MR-E was also more accurate in detecting a fibrotic component compared with PET/CT-E [p = 0.043] and with MR-E [p = 0.024]. Fibrosis was more frequently classified as inflammation with MR-E compared with PET/MR-E [p = 0.019]. Out of 8 patients with predominantly inflammatory CD who received medical treatment, 6 [75%] remained surgery free. Overall, 29 patients received surgery. At median follow-up of 9 [6-22] months, no recurrences occurred in either the medical or the surgical group. CONCLUSIONS Preoperative PET/MR-E imaging is highly accurate for assessing CD lesions before operation and contributed to clinical management of patients with small-bowel CD more often than PET/CT-E.
Collapse
Affiliation(s)
- Gianluca Pellino
- Unit of Colorectal Surgery, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy
| | | | - Onofrio A Catalano
- Department of Radiology, Harvard medical school, Massachusetts General Hospital, Boston, MA
| | - Severo Campione
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Francesco P D'Armiento
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | | | - Alberto Cuocolo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Francesco Selvaggi
- Unit of Colorectal Surgery, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy
| |
Collapse
|
|
38
|
Bettenworth D, Nowacki TM, Cordes F, Buerke B, Lenze F. Assessment of stricturing Crohn's disease: Current clinical practice and future avenues. World J Gastroenterol 2016; 22:1008-1016. [PMID: 26811643 PMCID: PMC4716016 DOI: 10.3748/wjg.v22.i3.1008] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 08/27/2015] [Accepted: 10/20/2015] [Indexed: 02/06/2023] Open
Abstract
Crohn’s disease (CD) is a chronic remittent idiopathic disease. Although the early phase of the disease is commonly characterized by inflammation-driven symptoms, such as diarrhea, the frequency of fibrostenotic complications in patients with CD increases over the long-term course of the disease. This review presents the current diagnostic options for assessing CD-associated strictures. In addition to the endoscopic evaluation of CD strictures, this review summarizes the currently available imaging modalities, including ultrasound and cross-sectional imaging techniques. In addition to stricture detection, differentiating between the primarily inflammatory strictures and the predominantly fibrotic ones is essential for selecting the appropriate treatment strategy (anti-inflammatory medical treatment vs endoscopical or surgical approaches). Therefore, recent imaging advances, such as contrast-enhanced ultrasound and ultrasound elastography, contribute to the development of non-invasive non-radiating imaging of CD-associated strictures. Finally, novel magnetic resonance imaging techniques, such as diffusion-weighted, motility and magnetization transfer imaging, as well as 18F-FDG PET/CT, molecular imaging approaches and biomarkers, are critically reviewed with regard to their potential role in assessing stricturing CD.
Collapse
|
|
39
|
Brückner M, Lenz P, Mücke MM, Gohar F, Willeke P, Domagk D, Bettenworth D. Diagnostic imaging advances in murine models of colitis. World J Gastroenterol 2016; 22:996-1007. [PMID: 26811642 PMCID: PMC4716050 DOI: 10.3748/wjg.v22.i3.996] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 09/09/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.
Collapse
|
|
40
|
Bernards N, Pottier G, Thézé B, Dollé F, Boisgard R. In vivo evaluation of inflammatory bowel disease with the aid of μPET and the translocator protein 18 kDa radioligand [18F]DPA-714. Mol Imaging Biol 2015; 17:67-75. [PMID: 25015387 PMCID: PMC4544644 DOI: 10.1007/s11307-014-0765-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Purpose The purpose of the study was to validate [18F]DPA-714, a translocator protein (TSPO) 18 kDa radioligand, as a probe to non-invasively quantify the inflammatory state in inflammatory bowel disease (IBD) animal models. Procedures Quantitative positron emission tomography (PET) imaging of intestinal inflammation was conducted with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) a glucose metabolism surrogate marker and [18F]DPA-714 a ligand of the 18 kDa TSPO, on two IBD models. The first model was induced using dextran sodium sulfate (DSS), creating global inflammation in the colon. The second model was induced by rectally administering trinitrobenzenesulfonic acid (TNBS), creating local and acute inflammation. Results The level of inflammation was analyzed using PET imaging on days 7 and 8. The analysis obtained with [18F]DPA-714, yielded a significant difference between the DSS treated (0.50 ± 0.17%ID/cc) and non-treated rats (0.35 ± 0.15%ID/cc). [18F]FDG on the other hand did not yield a significant difference. We did observe a mean glucose consumption in the colon increase from 0.40 ± 0.11 %ID/cc to 0.54 ± 0.17 %ID/cc. In the TNBS model, the uptake level of [18 F]DPA-714 increased significantly from 0.46 ± 0.23%ID/cc for the non-treated group, to 1.30 ± 0.62%ID/cc for those treated. PET signal was correlated with increased TSPO expression at cellular level. Conclusions Results indicate that [18F]DPA-714 is suitable for studying inflammation in IBD models. [18F]DPA-714 could be a good molecular probe to non-invasively evaluate the level and localization of inflammation. Moreover, in vivo imaging using this TSPO ligand is potentially a powerful tool to stage and certainly to follow the evolution and therapeutic efficiency at molecular level within this disease family.
Collapse
|
|
41
|
Wu Y, Briley K, Tao X. Nanoparticle-based imaging of inflammatory bowel disease. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY 2015; 8:300-15. [PMID: 26371464 DOI: 10.1002/wnan.1357] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Revised: 05/11/2015] [Accepted: 05/23/2015] [Indexed: 12/16/2022]
Affiliation(s)
- Yingwei Wu
- Department of Radiology; Shanghai Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine; Shanghai China
- Department of Radiology; Shanghai East Hospital, Tongji University, School of Medicine; Shanghai China
| | - Karen Briley
- Department of Radiology, Wright Center of Innovation and Biomedical Imaging; The Ohio State University; Columbus OH USA
| | - Xiaofeng Tao
- Department of Radiology; Shanghai Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine; Shanghai China
| |
Collapse
|
|
42
|
Hess S, Hansson SH, Pedersen KT, Basu S, Høilund-Carlsen PF. FDG-PET/CT in Infectious and Inflammatory Diseases. PET Clin 2014; 9:497-519, vi-vii. [PMID: 26050949 DOI: 10.1016/j.cpet.2014.07.002] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
|
|
43
|
Brückner M, Lenz P, Nowacki TM, Pott F, Foell D, Bettenworth D. Murine endoscopy for in vivo multimodal imaging of carcinogenesis and assessment of intestinal wound healing and inflammation. J Vis Exp 2014. [PMID: 25226434 DOI: 10.3791/51875] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Mouse models are widely used to study pathogenesis of human diseases and to evaluate diagnostic procedures as well as therapeutic interventions preclinically. However, valid assessment of pathological alterations often requires histological analysis, and when performed ex vivo, necessitates death of the animal. Therefore in conventional experimental settings, intra-individual follow-up examinations are rarely possible. Thus, development of murine endoscopy in live mice enables investigators for the first time to both directly visualize the gastrointestinal mucosa and also repeat the procedure to monitor for alterations. Numerous applications for in vivo murine endoscopy exist, including studying intestinal inflammation or wound healing, obtaining mucosal biopsies repeatedly, and to locally administer diagnostic or therapeutic agents using miniature injection catheters. Most recently, molecular imaging has extended diagnostic imaging modalities allowing specific detection of distinct target molecules using specific photoprobes. In conclusion, murine endoscopy has emerged as a novel cutting-edge technology for diagnostic experimental in vivo imaging and may significantly impact on preclinical research in various fields.
Collapse
Affiliation(s)
| | - Philipp Lenz
- Department of Medicine B, University Hospital Münster
| | | | | | - Dirk Foell
- Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster
| | | |
Collapse
|
|
44
|
Abstract
Functional imaging techniques enable physiological information to be derived, which, combined with high-resolution anatomical imaging, has the potential to improve the management of patients with intestinal disease. Two of the common pathologies where imaging has a substantial role in depicting disease extent, in staging disease, and assessing therapeutic response and/or disease relapse are cancer and inflammatory bowel disease. In these scenarios, functional imaging may augment assessment of disease activity, therapeutic response/non-response, as well as disease relapse by indicating physiological changes as a result of tumor, inflammation, or fibrosis.
Collapse
|
|
45
|
Turker NS, Heidari P, Kucherlapati R, Kucherlapati M, Mahmood U. An EGFR targeted PET imaging probe for the detection of colonic adenocarcinomas in the setting of colitis. Am J Cancer Res 2014; 4:893-903. [PMID: 25057314 PMCID: PMC4107290 DOI: 10.7150/thno.9425] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Accepted: 06/04/2014] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer is a serious complication associated with inflammatory bowel disease, often indistinguishable by screening with conventional FDG PET probes. We have developed an alternative EGFR-targeted PET imaging probe that may be used to overcome this difficulty, and successfully assessed its utility for neoplastic lesion detection in preclinical models. Cetuximab F(ab′)2 fragments were enzymatically generated, purified, and DOTA-conjugated. Radiolabeling was performed with 67Ga for cell based studies and 64Cu for in vivo imaging. Competitive binding studies were performed on CT26 cells to assess affinity (KD) and receptors per cell (Bmax). In vivo imaging using the EGFR targeted PET probe and 18F FDG was performed on CT26 tumor bearing mice in both control and dextran sodium sulfate (DSS) induced colitis settings. Spontaneous adenomas in genetically engineered mouse (GEM) models of colon cancer were additionally imaged. The EGFR imaging agent was generated with high purity (> 98%), with a labeling efficiency of 60 ± 5% and ≥99% radiochemical purity. The KD was 6.6 ± 0.7 nM and the Bmax for CT26 cells was 3.3 ± 0.1 × 106 receptors/cell. Target to background ratios (TBR) for CT26 tumors compared to colonic uptake demonstrated high values for both 18F-FDG (3.95 ± 0.13) and the developed 64Cu-DOTA-cetuximab-F(ab′)2 probe (4.42 ± 0.11) in control mice. The TBR for the EGFR targeted probe remained high (3.78 ± 0.06) in the setting of colitis, while for 18F FDG, this was markedly reduced (1.54 ± 0.08). Assessment of the EGFR targeted probe in the GEM models demonstrated a correlation between radiotracer uptake in spontaneous colonic lesions and the EGFR staining level ex vivo. A clinically translatable PET imaging probe was successfully developed to assess EGFR. The imaging agent can detect colonic tumors with a high TBR for detection of in situ lesions in the setting of colitis, and opens the possibility for a new approach for screening high-risk patients.
Collapse
|
|
46
|
New insight for the diagnosis of gastrointestinal acute graft-versus-host disease. Mediators Inflamm 2014; 2014:701013. [PMID: 24733964 PMCID: PMC3964897 DOI: 10.1155/2014/701013] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2013] [Accepted: 02/01/2014] [Indexed: 01/03/2023] Open
Abstract
Allogeneic stem cell transplantation (allo-SCT) is a curative therapy for different life-threatening malignant and nonmalignant hematologic disorders. Graft-versus-host disease (GVHD) remains a major source of morbidity and mortality following allo-SCT, which limits the use of this treatment in a broader spectrum of patients. Early diagnostic of GVHD is essential to initiate treatment as soon as possible. Unfortunately, the diagnosis of GVHD may be difficult to establish, because of the nonspecific nature of the associated symptoms and of the numerous differential diagnosis. This is particularly true regarding gastrointestinal (GI) acute GVHD. In the recent years many progress has been made in medical imaging test and endoscopic techniques. The interest of these different techniques in the diagnosis of GI acute GVHD has been evaluated in several studies. With this background we review the contributions, limitations, and future prospect of these techniques in the diagnosis of GI acute GVHD.
Collapse
|
|
47
|
FDG PET/CT in Crohn's disease: correlation of quantitative FDG PET/CT parameters with clinical and endoscopic surrogate markers of disease activity. Eur J Nucl Med Mol Imaging 2013; 41:605-14. [PMID: 24253895 DOI: 10.1007/s00259-013-2625-2] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Accepted: 10/31/2013] [Indexed: 02/08/2023]
Abstract
PURPOSE The aim of this study was to determine the feasibility and potential clinical utility of assessment of Crohn's disease (CD) activity by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT employing a new quantitative approach. METHODS A total of 22 subjects (mean age 37) with CD who had undergone FDG PET/CT followed by ileocolonoscopy within 1 week were included in this analysis. The CD endoscopy index of severity (CDEIS) for various bowel segments was calculated. The CD activity index (CDAI) was evaluated, and fecal calprotectin was measured. On PET, regions with increased FDG uptake in large bowel were segmented with an adaptive contrast-oriented thresholding algorithm, and metabolically active volume (MAV), uncorrected mean standardized uptake value (SUV(mean)), partial volume-corrected SUV(mean) (PVC-SUV(mean)), SUV(max), uncorrected total lesion glycolysis (TLG = MAV × SUV(mean)), and PVC total lesion glycolysis (PVC-TLG = MAV × PVC-SUV(mean)) were measured. Global CD activity score (GCDAS) was calculated as the sum of PVC-TLG over all clinically significant FDG-avid regions in each subject. Correlations between regional PET quantification measures (SUVs, TLGs) and CDEIS were calculated. Correlations between the global PET quantification measure (GCDAS, global SUVs) with CDAI, fecal calprotectin, CDEIS, and CRP level were also calculated. RESULTS SUV(max), PVC-SUV(mean), and PVC-TLG significantly correlated with segment CDEIS subscores (r = 0.50, r = 0.69, and r = 0.31, respectively; p < 0.05). GCDAS significantly correlated with CDAI and fecal calprotectin (r = 0.64 and r = 0.51, respectively; p < 0.05). CONCLUSION By employing this new quantitative approach, we were able to calculate indices of regional and global CD activity, which correlated well with both clinical and pathological disease activity surrogate markers. This approach may be of clinical importance in measuring both global disease activity and treatment response in patients with CD.
Collapse
|