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

Fingerprint

Positron emission tomography
Glucagon-Like Peptide 1
Positron-Emission Tomography
Peptides
peptides
mice
pancreas
positrons
Insulinoma
tomography
analogs
Imaging techniques
evaluation
Bearings (structural)
synthesis
cells
Keratin-19
Exocrine Pancreas
insulin
Amylases

ASJC Scopus subject areas

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

Cite this

Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging. / Behnam Azad, Babak; Rota, Vanessa; Yu, Lihai; McGirr, Rebecca; St. Amant, André H.; Lee, Ting Yim; Dhanvantari, Savita; Luyt, Leonard G.

In: Molecular Imaging, Vol. 14, No. 2, 01.04.2015.

Research output: Contribution to journalArticle

Behnam Azad, B, Rota, V, Yu, L, McGirr, R, St. Amant, AH, Lee, TY, Dhanvantari, S & Luyt, LG 2015, 'Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging', Molecular Imaging, vol. 14, no. 2. https://doi.org/10.2310/7290.2014.00057
Behnam Azad, Babak ; Rota, Vanessa ; Yu, Lihai ; McGirr, Rebecca ; St. Amant, André H. ; Lee, Ting Yim ; Dhanvantari, Savita ; Luyt, Leonard G. / Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging. In: Molecular Imaging. 2015 ; Vol. 14, No. 2.
@article{ebe110047f9a4bd9bdab5c959b0a9f33,
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.",
author = "{Behnam Azad}, Babak and Vanessa Rota and Lihai Yu and Rebecca McGirr and {St. Amant}, {Andr{\'e} H.} and Lee, {Ting Yim} and Savita Dhanvantari and Luyt, {Leonard G.}",
year = "2015",
month = "4",
day = "1",
doi = "10.2310/7290.2014.00057",
language = "English (US)",
volume = "14",
journal = "Molecular Imaging",
issn = "1535-3508",
publisher = "Decker Publishing",
number = "2",

}

TY - JOUR

T1 - Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging

AU - Behnam Azad, Babak

AU - Rota, Vanessa

AU - Yu, Lihai

AU - McGirr, Rebecca

AU - St. Amant, André H.

AU - Lee, Ting Yim

AU - Dhanvantari, Savita

AU - Luyt, Leonard G.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84928997163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928997163&partnerID=8YFLogxK

U2 - 10.2310/7290.2014.00057

DO - 10.2310/7290.2014.00057

M3 - Article

C2 - 25762192

AN - SCOPUS:84928997163

VL - 14

JO - Molecular Imaging

JF - Molecular Imaging

SN - 1535-3508

IS - 2

ER -