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

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

SUBMITTER: Yu Y

PROVIDER: S-EPMC6582641 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Yu Yanbo Y Liang Qianwa Q Liu Hui H Luo Zonghua Z Hu Hongzheng H Perlmutter Joel S JS Tu Zhude Z

Organic & biomolecular chemistry 20190601 22

The transient receptor potential channel subfamily member 5 (TRPC5) is a calcium permeable cation channel widely expressed in the brain. Accumulating evidence indicates that it plays a crucial role in psychiatric disorders including depression and anxiety. Positron emission tomography (PET) combined with a TRPC5 specific radioligand may provide a unique tool to investigate the functions of TRPC5 in animal disease models to guide drug development targeting TRPC5. To develop a TRPC5 PET radiotrace ...[more]

PMID: 31115430

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

Publications

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

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