Synthesis of GPR40 targeting ³H- and ¹⁸F-probes towards selective beta cell imaging

authored by

Romain Bertrand, Isabel Hamp, Mark Brönstrup, Remo Weck, Mario Lukacevic, Andras Polyak, Tobias L. Ross, Martin Gotthardt, Oliver Plettenburg, Volker Derdau

Abstract

Diabetes affects an increasing number of patients worldwide and is responsible for a significant rise in healthcare expenses. Imaging of β-cells in vivo is expected to contribute to an improved understanding of the underlying pathophysiology, improved diagnosis, and development of new treatment options for diabetes. Here, we describe the first radiosyntheses of [³H]-TAK875 and [¹⁸F]-TAK875 derivatives to be used as β-cell imaging probes addressing the free fatty acid receptor 1 (FFAR1/GPR40). The fluorine-labeled derivative showed similar agonistic activity as TAK875 in a functional assay. The radiosynthesis of the ¹⁸F-labelled tracer 2a was achieved with 16.7 ± 5.7% radiochemical yield in a total synthesis time of 60–70 min.

Organisation(s)

Institute of Organic Chemistry

External Organisation(s)

Sanofi-Aventis Deutschland GmbH
Radboud University Nijmegen (RU)
Helmholtz Centre for Infection Research (HZI)
Hannover Medical School (MHH)
Helmholtz Zentrum München - German Research Center for Environmental Health

Type

Article

Journal

Journal of Labelled Compounds and Radiopharmaceuticals

Volume

59

Pages

604-610

No. of pages

7

ISSN

0362-4803

Publication date

01.12.2016

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Analytical Chemistry, Biochemistry, Radiology Nuclear Medicine and imaging, Drug Discovery, Spectroscopy, Organic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1002/jlcr.3412 (Access: Closed)