Radiosynthesis of a carbon-11 labeled tetrahydrobenzisoxazole derivative as a new PET probe for γ-secretase imaging in Alzheimer's disease

To develop PET radiotracers for imaging of Alzheimer's disease, a new carbon-11 labeled potent and selective gamma-secretase modulator (GSM) has been synthesized. The reference standard tetrahydrobenzisoxazole derivative 8 and its desmethylated precursor 9 were synthesized from cyclohex-2-en-l-one and 3-hydroxy-4-nitrobenzaldehyde in eight and nine steps with 11% and 5% overall chemical yield, respectively. The radiotracer [C-11]8 was prepared from its corresponding precursor 9 with [C-11]CH3OTf through O-C-11-methylation and isolated by RP-HPLC combined with SPE in 45-50% radiochemical yield, based on [C-11]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (A(m)) at EOB was 555-740 GBq/mu mol.