Synthesis And Characterization Of Carbon-11 Labeled Iloperidone For Imaging Of Alpha(1)-Adrenoceptor In Brain

alpha(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 alpha(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 alpha(1)-adrenoceptor and moderate selectivity over other brain receptors. We report herein the synthesis and characterization of carbon-11 labeled iloperidone for imaging of alpha(1)-adrenoceptor in brain. The radiolabeling of [C-11]iloperidone was carried out conveniently in one step by treating precursor with [C-11]CH3I in DMF in the presence of K2CO3. Then, [C-11]iloperidone was purified by semi-preparative HPLC, and characterized in C57BL/6 mice using PET/CT scanning. The desired product [C-11]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/mu mol with total synthetic time of 35-40 min. PET/CT scanning in C57BL/6 mice showed favorable pharmacokinetic properties and high brain exposure of [C-11]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 [C-11]iloperidone can serve as a lead compound for the further development of specific radiotracers for PET imaging of alpha(1)-adrenoceptor in brain clinically.