Targeted Optical Imaging of the Glucagonlike Peptide 1 Receptor Using Exendin-4-IRDye 800CW
| Autor: | Gooitzen M. van Dam, Maarten Brom, Martin Gotthardt, Sanne A. M. van Lith, François Pattou, Mijke Buitinga, Camille Marciniak, Selen Ekim, Marti Boss, Gerwin Sandker, Cathelijne Frielink, Desiree Bos |
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| Přispěvatelé: | Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Microbes in Health and Disease (MHD), Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Rok vydání: | 2020 |
| Předmět: |
Fluorescence-lifetime imaging microscopy
Pathology Indoles Swine 030218 nuclear medicine & medical imaging Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] Mice 0302 clinical medicine Endocrinology Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] Fluorescence microscope Tissue Distribution Chemistry Benzenesulfonates digestive oral and skin physiology LOCALIZATION exendin medicine.anatomical_structure 030220 oncology & carcinogenesis SURGICAL-TREATMENT Female fluorescence medicine.symptom Pancreas hormones hormone substitutes and hormone antagonists BETA-CELL MASS Biodistribution medicine.medical_specialty endocrine system PET/CT Mice Nude CHO Cells DIAGNOSIS Glucagon-Like Peptide-1 Receptor Lesion 03 medical and health sciences optical imaging congenital hyperinsulinism All institutes and research themes of the Radboud University Medical Center Cricetulus In vivo medicine Animals Radiology Nuclear Medicine and imaging Basic Insulinoma Pancreatic islets Other Research Radboud Institute for Health Sciences [Radboudumc 0] Biological Transport medicine.disease INSULINOMA Exenatide Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] FLUORESCENCE-GUIDED SURGERY |
| Zdroj: | The Journal of Nuclear Medicine (1978), 61, 1066-1071 Journal of Nuclear Medicine, 61(7), 1066-1071. SOC NUCLEAR MEDICINE INC Journal of Nuclear Medicine The Journal of Nuclear Medicine (1978), 61, 7, pp. 1066-1071 |
| ISSN: | 0161-5505 |
| Popis: | The treatment of choice for insulinomas and focal lesions in congenital hyperinsulinism (CHI) is surgery. However, intraoperative detection can be challenging. This challenge could be overcome with intraoperative fluorescence imaging, which provides real-time lesion detection with a high spatial resolution. Here, a novel method for targeted near-infrared (NIR) fluorescence imaging of glucagonlike peptide 1 receptor (GLP-1R)-positive lesions, using the GLP-1 agonist exendin-4 labeled with IRDye 800CW, was examined in vitro and in vivo. Methods: A competitive binding assay was performed using Chinese hamster lung (CHL) cells transfected with GLP-1R. Tracer biodistribution was determined in BALB/c nude mice bearing subcutaneous CHL-GLP-1R xenografts. In vivo NIR fluorescence imaging of CHL-GLP-1R xenografts was performed. Localization of the tracer in the pancreatic islets of BALB/c nude mice was examined using fluorescence microscopy. Laparoscopic imaging was performed to detect the fluorescent signal of the tracer in the pancreas of mini pigs. Results: Exendin-4-IRDye 800CW binds GLP-1R with a half-maximal inhibitory concentration of 3.96 nM. The tracer accumulates in CHL-GLP-1R xenografts. Subcutaneous CHL-GLP-1R xenografts were visualized using in vivo NIR fluorescence imaging. The tracer accumulates specifically in the pancreatic islets of mice, and a clear fluorescent signal was detected in the pancreas of mini pigs. Conclusion: These data provide the first in vivo evidence of the feasibility of targeted fluorescence imaging of GLP-1R-positive lesions. Intraoperative lesion delineation using exendin-4-IRDye 800CW could benefit open as well as laparoscopic surgical procedures for removal of insulinomas and focal lesions in CHI. |
| Databáze: | OpenAIRE |
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