Edgar Fraser Graeme, Hansen Hanne D, Leth-Petersen Sebastian, Ettrup Anders, Kristensen Jesper L, Knudsen Gitte M, Herth Matthias M
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.
J Labelled Comp Radiopharm. 2017 Oct;60(12):586-591. doi: 10.1002/jlcr.3557. Epub 2017 Sep 18.
An agonist PET tracer is of key interest for the imaging of the 5-HT receptor, as exemplified by the previously reported success of [ C]Cimbi-36. Fluorine-18 holds several advantages over carbon-11, making it the radionuclide of choice for clinical purposes. In this respect, an F-labelled agonist 5-HT receptor (5-HT R) tracer is highly sought after. Herein, we report a 2-step, 1-pot labelling methodology of 2 tracer candidates. Both ligands display high in vitro affinities for the 5-HT R. The compounds were synthesised from easily accessible labelling precursors, and radiolabelled in acceptable radiochemical yields, sufficient for in vivo studies in domestic pigs. PET images partially conformed to the expected brain distribution of the 5-HT R; a notable exception however being significant uptake in the striatum and thalamus. Additionally, a within-scan displacement challenge with a 5-HT R antagonist was unsuccessful, indicating that the tracers cannot be considered optimal for neuroimaging of the 5-HT R.
激动剂正电子发射断层扫描（PET）示踪剂对于5-羟色胺（5-HT）受体成像至关重要，之前报道的[C]Cimbi-36的成功便是例证。氟-18相对于碳-11具有若干优势，使其成为临床应用的首选放射性核素。在这方面，一种氟标记的激动剂5-HT受体（5-HT R）示踪剂备受追捧。在此，我们报告了两种示踪剂候选物的两步一锅法标记方法。两种配体对5-HT R均显示出高体外亲和力。这些化合物由易于获取的标记前体合成，并以可接受的放射化学产率进行放射性标记，足以用于家猪的体内研究。PET图像部分符合5-HT R预期的脑部分布；然而，一个显著的例外是纹状体和丘脑有明显摄取。此外，用5-HT R拮抗剂进行的扫描内置换激发未成功，这表明这些示踪剂不能被认为是用于5-HT R神经成像的最佳选择。
