Radiosynthesis and in vivo evaluation of [11C]MOV as a PET imaging agent for COX-2 |
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Authors: | Jaya Prabhakaran Mark Underwood Francesca Zanderigo Norman R Simpson Anna R Cooper Jeffrey Matthew Harry Rubin-Falcone Ramin V Parsey J John Mann JS Dileep Kumar |
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Institution: | 1. Department of Psychiatry, Columbia University Medical Center, New York, USA;2. Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, USA;3. Department of Psychiatry, Stony Brook Medical Center, Stony Brook, New York, USA |
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Abstract: | Radiosynthesis and in vivo evaluation of 11C]4-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (methoxy analogue of valdecoxib, 11C]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 11C]MOV was accomplished in 40?±?10% yield and?>99% radiochemical purity by reacting the precursor 2 in dimethyl formamide (DMF) with 11C]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 11C]MOV in brain. The radioligand underwent rapid metabolism in baboon plasma. MicroPET studies in male Sprague Dawley rats revealed 11C]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. |
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Keywords: | PET Inflammation COX-2 Radiotracer |
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