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

Radiosynthesis and in vivo evaluation of [C-11]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (methoxy analogue of valdecoxib, [C-11]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 [C-11]MOV was accomplished in 40 +/- 10% yield and > 99% radiochemical purity by reacting the precursor 2 in dimethyl formamide (DMF) with [C-11] CH3I 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 [C-11]MOV in brain. The radioligand underwent rapid metabolism in baboon plasma. MicroPET studies in male Sprague Dawley rats revealed [C-11]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.