Radiosynthesis and evaluation of an 18F\u2013labeled silicon containing exendin-4 peptide as a PET probe for imaging insulinoma

Lukas O Dialer,Roger Schibli,Simon M Ametamey,Andreas Jodal,Martin Béhé

doi:10.1186/s41181-017-0036-6

Lukas O Dialer, Roger Schibli + Show 3 more

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https://doi.org/10.1186/s41181-017-0036-6

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Abstract

BackgroundAnalogues of exendin-4 have been radiolabeled for imaging the glucagon-like peptide type 1 receptors (GLP-1R) which are overexpressed in insulinoma. The aim of this research was to synthesize an 18F–labeled silicon containing exendin-4 peptide (18F-2) and to evaluate its in vitro and in vivo behavior in CHL-GLP-1 receptor positive tumor-bearing mice.18F–labeled silicon containing exendin-4 peptide (18F-2) was prepared via one-step nucleophilic substitution of a silane precursor with 18F–fluoride in the presence of acetic acid and K222. 18F-2 was then administered to tumor-bearing mice for PET imaging and ex vivo biodistribution experiments.Results18F-2 was produced in a radiochemical yield (decay corrected) of 1.5% and a molar activity of max. 16 GBq/μmol. The GLP-1R positive tumors were clearly visualized by PET imaging. Biodistribution studies showed reduced uptake of 18F-2 in the kidneys compared to radiometal labeled exendin-4 derivatives. The radiotracer showed specific tumour uptake which remained steady over 2 h.ConclusionsThis exendin-4 analogue, 18F-2, is a potential probe for imaging GLP-1R positive tumors.

Highlights

Analogues of exendin-4 have been radiolabeled for imaging the glucagon-like peptide type 1 receptors (GLP-1R) which are overexpressed in insulinoma
We evaluated an exendin-4 analogue, modified with a silicon containing building block, in order to elucidate its potential as an imaging agent for targeting GLP-1R positive insulinoma
We reasoned that by incorporating the rather highly lipophilic di-tert-butylphenylsilane building block in exendin-4, we could significantly reduce the kidney uptake and thereby shift renal to hepatobiliary clearance

Summary

Introduction

Analogues of exendin-4 have been radiolabeled for imaging the glucagon-like peptide type 1 receptors (GLP-1R) which are overexpressed in insulinoma. The aim of this research was to synthesize an 18F–labeled silicon containing exendin-4 peptide (18F-2) and to evaluate its in vitro and in vivo behavior in CHL-GLP-1 receptor positive tumor-bearing mice. 18F–labeled silicon containing exendin-4 peptide (18F-2) was prepared via one-step nucleophilic substitution of a silane precursor with 18F–fluoride in the presence of acetic acid and K222. 18F-2 was administered to tumor-bearing mice for PET imaging and ex vivo biodistribution experiments The aim of this research was to synthesize an 18F–labeled silicon containing exendin-4 peptide (18F-2) and to evaluate its in vitro and in vivo behavior in CHL-GLP-1 receptor positive tumor-bearing mice. 18F–labeled silicon containing exendin-4 peptide (18F-2) was prepared via one-step nucleophilic substitution of a silane precursor with 18F–fluoride in the presence of acetic acid and K222. 18F-2 was administered to tumor-bearing mice for PET imaging and ex vivo biodistribution experiments

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