Development of a carbon-11 PET radiotracer for imaging TRPC5 in the brain

• DOI: 10.1039/c9ob00893d
• Publication Date: 2019-05-09T16:55:34Z
• Authors: Yanbo Yu; Qianwa Liang; Hui Liu; Zonghua Luo; Hongzheng Hu; Joel S. Perlmutter; Zhude Tu
• Keywords: PET Imaging; TRPC5

The transient receptor potential channel subfamily member 5 (TRPC5) is a calcium permeable cation widely expressed in the brain. Accumulating evidence indicates that it plays crucial role psychiatric disorders including depression and anxiety. Positron emission tomography (PET) combined with TRPC5 specific radioligand may provide unique tool to investigate functions of animal disease models guide drug development targeting TRPC5. To develop PET radiotracer, potent inhibitor HC608 was chosen for C-11 radiosynthesis through N-demethyl amide precursor 7 reacting [11C]methyl iodide. Under optimized conditions, [11C]HC608 achieved good radiochemical yield (25 ± 5%), high chemical purity (>99%), activity (204-377 GBq μmol-1, decay corrected end bombardment, EOB). vitro autoradiography study revealed specifically binds Moreover, initial vivo evaluation performed rodents microPET brain non-human primates further demonstrated able penetrate blood barrier sufficiently accumulate These results suggest has be tracer imaging vivo.