[¹¹C]Dimebon as a new PET agent for imaging of Alzheimer’s disease and Huntington’s disease

Objectives Dimebon is an antihistamine drug that has been developed and used in Russia since 1983. This old drug has been recently proposed to be useful for treating neurodegenerative disorders such as Alzheimer’s disease (AD) and Huntington’s disease (HD). This study was designed to develop [¹¹C]Dimebon as a new PET agent for imaging of AD and HD.

Methods The reference standard Dimebon {2,8-dimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole} and its corresponding desmethylated precursor 8-dimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole were synthesized from p-toluidine, 2-methyl-5-vinylpyridine and substituted piperidin-4-one in 4 steps including 1,2-addition, nitration, reduction and condensation reactions. The target tracer [¹¹C]Dimebon was prepared from its precursor with [¹¹C]CH₃OTf under basic condition through N-[¹¹C]methylation and isolated by HPLC method.

Results The overall chemical yields for the target compound and the precursor in 4 steps were 33% and 30% respectively. The radiochemical yield for the target tracer was 30-40%, decay corrected to end of bombardment (EOB), based on [¹¹C]CO₂. The specific activity was 222-296 GBq/μmol at EOB.

Conclusions A new synthetic route to labeling precursor and Dimebon has been described, and an efficient and convenient synthesis of [¹¹C]Dimebon has been well-developed for the first time.

Research Support The Indiana Genomics Initiative (INGEN) of Indiana University, which is supported in part by Lilly Endowment Inc