Bertrand Romain, Hamp Isabel, Brönstrup Mark, Weck Remo, Lukacevic Mario, Polyak Andras, Ross Tobias L, Gotthardt Martin, Plettenburg Oliver, Derdau Volker
Diabetes Division, Research & Translational Medicine, Sanofi GmbH, Frankfurt am Main, Germany.
Department of Nuclear Medicine, Radboud UMC, Nijmegen, The Netherlands.
J Labelled Comp Radiopharm. 2016 Dec;59(14):604-610. doi: 10.1002/jlcr.3412. Epub 2016 Jun 10.
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 [ H]-TAK875 and [ F]-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 F-labelled tracer 2a was achieved with 16.7 ± 5.7% radiochemical yield in a total synthesis time of 60-70 min.
糖尿病在全球影响着越来越多的患者，并导致医疗费用大幅上升。体内β细胞成像有望有助于更好地理解潜在的病理生理学，改善糖尿病的诊断，并开发新的治疗方案。在此，我们描述了[H]-TAK875和[F]-TAK875衍生物的首次放射性合成，它们将用作针对游离脂肪酸受体1（FFAR1/GPR40）的β细胞成像探针。在功能测定中，氟标记的衍生物显示出与TAK875相似的激动活性。F标记示踪剂2a的放射性合成在60-70分钟的总合成时间内以16.7±5.7%的放射化学产率实现。
