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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalMolecular imaging
Volume14
Issue number2
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

Cite this

Azad, B. B., Rota, V., Yu, L., McGirr, R., St. Amant, A. H., Lee, T. Y., Dhanvantari, S., & Luyt, L. G. (2015). Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging. Molecular imaging, 14(2). https://doi.org/10.2310/7290.2014.00057