Synthesis of GPR40 targeting3H- and18F-probes towards selective beta cell imaging.
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 the18F-labelled tracer 2a was achieved with 16.7 ± 5.7% radiochemical yield in a total synthesis time of 60-70 min.
Diabetes Division, Research & Translational Medicine, Sanofi GmbH, Frankfurt am Main, Germany.|Department of Nuclear Medicine, Radboud UMC, Nijmegen, The Netherlands.
Romain
R
Bertrand
Diabetes Division, Research & Translational Medicine, Sanofi GmbH, Frankfurt am Main, Germany.
Isabel
I
Hamp
Diabetes Division, Research & Translational Medicine, Sanofi GmbH, Frankfurt am Main, Germany.|Helmholtz Centre for Infection Research, Braunschweig, Germany.
Mark
M
Brönstrup
DSAR/Drug Disposition, Sanofi GmbH, Frankfurt am Main, Germany.
Remo
R
Weck
Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Mario
M
Lukacevic
Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Andras
A
Polyak
Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Tobias L
TL
Ross
Department of Nuclear Medicine, Radboud UMC, Nijmegen, The Netherlands.
Martin
M
Gotthardt
Diabetes Division, Research & Translational Medicine, Sanofi GmbH, Frankfurt am Main, Germany.|Institute of Medicinal Chemistry, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, Neuherberg DE-85764, Germany.|Leibniz Universität Hannover, Schneiderberg 1b, 30167, Hannover, Germany.
Oliver
O
Plettenburg
DSAR/Drug Disposition, Sanofi GmbH, Frankfurt am Main, Germany.
Volker
V
Derdau
D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D060326:Chemistry Techniques, Synthetic; D005462:Fluorine Radioisotopes; D057809:HEK293 Cells; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D014316:Tritium
D001572:Benzofurans; C473034:FFAR1 protein, human; D005462:Fluorine Radioisotopes; D043562:Receptors, G-Protein-Coupled; D013450:Sulfones; C557331:TAK-875; D014316:Tritium
GPR40; beta cell imaging; fluorine-18; tritium