Indirectly radioiodinated exendin-4 as an analytical tool for in vivo detection of glucagon-like peptide-1 receptor in a disease setting
| Autor: | Masahiko Hirata, Naoya Kondo, Takashi Temma, Ayaka Oishi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Agonist
endocrine system medicine.drug_class Peptide Glucagon-Like Peptide-1 Receptor 030218 nuclear medicine & medical imaging Iodine Radioisotopes Mice 03 medical and health sciences 0302 clinical medicine In vivo Cell Line Tumor Animals Humans Medicine Disease Radiology Nuclear Medicine and imaging Receptor Insulinoma chemistry.chemical_classification business.industry digestive oral and skin physiology General Medicine medicine.disease Glucagon-like peptide-1 Molecular biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Exenatide business Pancreas hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Annals of Nuclear Medicine. 35:83-91 |
| ISSN: | 1864-6433 0914-7187 |
| DOI: | 10.1007/s12149-020-01540-0 |
| Popis: | Glucagon-like peptide-1 receptor agonist (GLP-1RA) has been reported to have therapeutic effects on diabetes and various diseases. Precise detection of GLP-1 receptor (GLP-1R) can be useful to diagnose and elucidate the mechanism of such diseases. Here we aimed to develop an imaging probe based on GLP-1RA that has high molar activity and sensitivity for detection of low-level GLP-1R expression in non-pancreatic diseases. We selected the agonist exenatide (Ex4) as the parent peptide of a GLP-1R targeting probe and prepared Cys-Ex4 by addition of an N-terminal Cys residue and labeling with the prosthetic agent N-(3-[125I]iodophenyl)maleimide ([125I]IPM) to generate [125I]Ex4ipm. We evaluated the affinity of [125I]Ex4ipm for GLP-1R, as well as cellular binding profiles in insulinoma and prostate cancer cell lines, and in vivo biodistributions in normal and tumor-bearing mice to assess GLP-1R-dependent accumulation of radioactivity in tissues. [125I]Ex4ipm was easily synthesized with high radiochemical yield (73%), radiochemical purity (> 99%), and molar activity (81 GBq/µmol) via a thiol/maleimide reaction. Following administration to mice, [125I]Ex4ipm accumulated to high levels in the pancreas (23.3% ID/g), with radioactivity co-localizing in areas having insulin-positive β cells. High amounts of radioactivity also accumulated in insulinomas that overexpressed GLP-1R (27.5% ID/g). In contrast, low amounts of [125I]Ex4ipm accumulation, corresponding to low expression levels of GLP-1R, were observed in prostate cancer cells and xenografts used as a model of non-pancreatic applications. Our results suggested that [123I]Ex4ipm could be valuable for GLP-1R imaging in diabetes, insulinomas, and various diseases related to GLP-1R. |
| Databáze: | OpenAIRE |
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