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Open Access 01-12-2016 | Original research

Low kidney uptake of GLP-1R-targeting, beta cell-specific PET tracer, ¹⁸F-labeled [Nle¹⁴,Lys⁴⁰]exendin-4 analog, shows promise for clinical imaging

Authors: Kirsi Mikkola, Cheng-Bin Yim, Paula Lehtiniemi, Saila Kauhanen, Miikka Tarkia, Tuula Tolvanen, Pirjo Nuutila, Olof Solin

Published in: EJNMMI Research | Issue 1/2016

Abstract

Background

Several radiometal-labeled, exendin-based tracers that target glucagon-like peptide-1 receptors (GLP-1R) have been intensively explored for β cell imaging. The main obstacle has been the high uptake of tracer in the kidneys. This study aimed to develop a novel GLP1-R-specific tracer, with fluorine-18 attached to exendin-4, to label β cells for clinical imaging with PET (positron emission tomography). We hypothesized that this tracer would undergo reduced kidney uptake. ¹⁸F-labeled [Nle¹⁴,Lys⁴⁰]exendin-4 analog ([¹⁸F]exendin-4) was produced via Cu-catalyzed click chemistry. The biodistribution of [¹⁸F]exendin-4 was assessed with ex vivo organ γ-counting and in vivo PET imaging. We also tested the in vivo stability of the radiotracer. The localization of ¹⁸F radioactivity in rat and human pancreatic tissue sections was investigated with autoradiography. Receptor specificity was assessed with unlabeled exendin-3. Islet labeling was confirmed with immunohistochemistry. The doses of radiation in humans were estimated based on biodistribution results in rats.

Results

[¹⁸F]exendin-4 was synthesized with high yield and high specific activity. Results showed specific, sustained [¹⁸F]exendin-4 uptake in pancreatic islets. In contrast to previous studies that tested radiometal-labeled exendin-based tracers, we observed rapid renal clearance of [¹⁸F]exendin-4.

Conclusions

[¹⁸F]exendin-4 showed promise as a tracer for clinical imaging of pancreatic β cells, due to its high specific uptake in native β cells and its concomitant low kidney radioactivity uptake.

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Title: Low kidney uptake of GLP-1R-targeting, beta cell-specific PET tracer, 18F-labeled [Nle14,Lys40]exendin-4 analog, shows promise for clinical imaging
Authors: Kirsi Mikkola
Cheng-Bin Yim
Paula Lehtiniemi
Saila Kauhanen
Miikka Tarkia
Tuula Tolvanen
Pirjo Nuutila
Olof Solin
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2016
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-016-0243-2

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Low kidney uptake of GLP-1R-targeting, beta cell-specific PET tracer, ¹⁸F-labeled [Nle¹⁴,Lys⁴⁰]exendin-4 analog, shows promise for clinical imaging

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Results

Conclusions

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