Radiosynthesis and in vivo evaluation of [ 11 C]MOV as a PET imaging agent for COX-2

Abstract Radiosynthesis and in vivo evaluation of [ 11 C]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1 H -pyrazol-1-yl]benzenesulfonamide (methoxy analogue of valdecoxib, [ 11 C]MOV), a COX-2 inhibitor, was conducted in rat and baboon. Synthesis of the reference standard MOV ( 3 ), and its desmethyl precursor 2 for radiolabeling were performed using 1,2-diphenylethan-1-one as the starting material in five steps with 15% overall yield. Radiosynthesis of [ 11 C]MOV was accomplished in 40 ± 10% yield and >99% radiochemical purity by reacting the precursor 2 in dimethyl formamide (DMF) with [ 11 C]CH 3 I followed by removal of the dimethoxytrityl (DMT) protective group using trifluroacetic acid. PET studies in anesthetized baboon showed very low uptake and homogeneous distribution of [ 11 C]MOV in brain. The radioligand underwent rapid metabolism in baboon plasma. MicroPET studies in male Sprague Dawley rats revealed [ 11 C]MOV binding in lower thorax. The tracer binding in rats was partially blocked in heart and duodenum by the administration of 1 mg/kg oral dose of COX-2 inhibitor valdecoxib.