Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R Imaging

Babak Behnam Azad; Vanessa Rota; Lihai Yu; Rebecca Mcgirr; André H. St. Amant; Ting-Yim Lee; Savita Dhanvantari; Leonard G. Luyt PhD

doi:10.2310/7290.2014.00057

Molecular Imaging (Jan 2015)

Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R Imaging

Babak Behnam Azad,
Vanessa Rota,
Lihai Yu,
Rebecca Mcgirr,
André H. St. Amant,
Ting-Yim Lee,
Savita Dhanvantari,
Leonard G. Luyt PhD

Affiliations

Babak Behnam Azad: Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.
Vanessa Rota: Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.
Lihai Yu: Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.
Rebecca Mcgirr: Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.
André H. St. Amant: Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.
Ting-Yim Lee: Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.
Savita Dhanvantari: Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.
Leonard G. Luyt PhD: Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.

DOI: https://doi.org/10.2310/7290.2014.00057
Journal volume & issue: Vol. 14

Abstract

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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 68 Ga-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.

Published in Molecular Imaging

ISSN: 1536-0121 (Online)
Publisher: SAGE Publishing
Country of publisher: United States
LCC subjects: Science: Biology (General); Medicine: Medicine (General): Medical technology
Website: https://journals.sagepub.com/home/MIX

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