title: Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging.
abstract: A fluorescein-GLP-1 (7-37) analog was generated to determine GLP-1R distribution in various cell types of the pancreas in both strains of mice and receptor-specific uptake was confirmed by blocking with exendin-4. Biodistribution studies were carried out using 68Ga-labeled GLP-1(7-37) peptides in CD1 and C57BL/6 mice. In addition, immunocompromised mice bearing GLP-1R-expressing insulinomas were evaluated by positron emission tomography (PET) imaging and ex vivo biodistribution studies. The optical GLP-1 probe strongly colocalized with immunofluorescence for insulin and glucagon, and more weakly with amylase (exocrine pancreas) and cytokeratin 19 (ductal cells), confirming its application for in situ GLP-1R imaging in various pancreatic cell types. Insulinomas were clearly visualized by in vivo PET. Reducing the peptide positive charge decreased renal retention as well as tumor uptake. Results demonstrate the application of the developed GLP-1 peptide analogues for in situ (optical) and in vivo (PET) imaging of GLP-1R expression.
authors.forename: Babak
authors.initials: B
authors.lastname: Behnam Azad
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rota
authors.forename: Lihai
authors.initials: L
authors.lastname: Yu
authors.forename: Rebecca
authors.initials: R
authors.lastname: McGirr
authors.forename: André H
authors.initials: AH
authors.lastname: St Amant
authors.forename: Ting-Yim
authors.initials: TY
authors.lastname: Lee
authors.forename: Savita
authors.initials: S
authors.lastname: Dhanvantari
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Luyt
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D005708:Gallium / Q000737:chemistry; D005710:Gallium Radioisotopes / Q000737:chemistry; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007340:Insulinoma / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging; D009368:Neoplasm Transplantation; D010455:Peptides / Q000737:chemistry*; D049268:Positron-Emission Tomography; D011863:Radioimmunoassay
chemical_list: D005710:Gallium Radioisotopes; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010455:Peptides; D052216:Glucagon-Like Peptide 1; D005708:Gallium; D000242:Cyclic AMP; D005947:Glucose