Synthesis and Characterization of Carbon-11 Labeled Iloperidone for Imaging of α(1)-Adrenoceptor in Brain

α(1)-Adrenoceptor is implicated in numerous neuronal diseases. The development of new modulators targeting this receptor as well as the investigation of the role of α(1)-adrenoceptor in healthy and disease conditions, however, is hindered by the lack of specific positron emission tomography (PET) radiotracers. Iloperidone shows a high binding affinity to α(1)-adrenoceptor and moderate selectivity over other brain receptors. We report herein the synthesis and characterization of carbon-11 labeled iloperidone for imaging of α(1)-adrenoceptor in brain. The radiolabeling of [(11)C]iloperidone was carried out conveniently in one step by treating precursor with [(11)C]CH(3)I in DMF in the presence of K(2)CO(3). Then, [(11)C]iloperidone was purified by semi-preparative HPLC, and characterized in C57BL/6 mice using PET/CT scanning. The desired product [(11)C]iloperidone was obtained in an average decay corrected radiochemical of 12% (n = 3) and over 99% radiochemical purity. The average molar radioactivity was 357 GBq/μmol with total synthetic time of 35–40 min. PET/CT scanning in C57BL/6 mice showed favorable pharmacokinetic properties and high brain exposure of [(11)C]iloperidone. Blocking experiments by pretreatment with the unlabeled iloperidone showed the significant blocking effects with about 25% reduction in brain uptake. These results suggested that [(11)C]iloperidone can serve as a lead compound for the further development of specific radiotracers for PET imaging of α(1)-adrenoceptor in brain clinically.