TY - JOUR

T1 - Synthesis of GPR40 targeting 3H- and 18F-probes towards selective beta cell imaging

AU - Bertrand, Romain

AU - Hamp, Isabel

AU - Brönstrup, Mark

AU - Weck, Remo

AU - Lukacevic, Mario

AU - Polyak, Andras

AU - Ross, Tobias L.

AU - Gotthardt, Martin

AU - Plettenburg, Oliver

AU - Derdau, Volker

N1 - Funding Information: The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007–2013/ under REA grant agreement no. 289932. We acknowledge Ute Messinger and Jenny Schubert for their help with providing analytical data, Juergen Dedio, Birgit Herzog, Inge Kress-Fischer, and Matthias Lohmann for performing the FLIPR Ca

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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.

KW - beta cell imaging

KW - fluorine-18

KW - GPR40

KW - tritium

UR - http://www.scopus.com/inward/record.url?scp=84994259783&partnerID=8YFLogxK

U2 - 10.1002/jlcr.3412

DO - 10.1002/jlcr.3412

M3 - Article

C2 - 27282912

AN - SCOPUS:84994259783

VL - 59

SP - 604

EP - 610

JO - Journal of Labelled Compounds and Radiopharmaceuticals

JF - Journal of Labelled Compounds and Radiopharmaceuticals

SN - 0362-4803

IS - 14

ER -