A CONVENIENT RADIOLABELING OF [C-11](R)-PK11195 USING LOOP METHOD IN AUTOMATIC SYNTHESIS MODULE

Abstract

Objectives: The [11C](R)-PK11195 ((R)-1-(2-chlorophenyl)-N-1-[11C]methyl-N-(1-propyl)-3-isoquinoline carboxamide), is a specific ligand for the peripheral type benzodiazepine receptor and a marker of activated microglia, used to measure inflammation in neurologic disorders. We report here that a more direct and simpler radiosynthesis of [11C](R)-PK11195 in mild condition is possible with NaH suspension and an one-steploop method for the automated synthesis module. Direct radiolabeling of the amide nitrogen with NaH suspension results in [11C](R)-PK11195 with good yields. Methods: In Automated radiosynthesis module, 1 mg of (R)-N-Desmethyl-PK11195 in 0.1 mL DMSO and NaH suspension 0.1 mL injected at radiosynthesis module, [11C]methyl iodide passed through HPLC loop at room temperature (RT). The reaction mixture was separated by semi-preparative HPLC. Aliquots eluted at 11.3 min were collected and analyzed by analytical HPLC and mass spectrometer. Results: The labeling efficiency of [11C](R)-PK11195 was 71.8±8.5 percent, The specific radioactivity was 11.8±6.4 GBq/μmol, and The chemical and radiochemical purity were higher than 99.2%. The mass spectrum of the product eluted at 11.3 min showed m/z peaks at 353.1 (M+1), indicating the mass and structure of (R)-PK11195. Conclusions: By the one-step loop method with the [11C]CH3I automated synthesis module, [11C](R)-PK11195 could be simply prepared in high radiochemical yields with using NaH suspension. Also, the method can be successfully applied for routine clinical application, proved to be a simplified alternative to the bubbling method and offered an easy way to transfer the reaction mixture into an HPLC column.