Synthesis and in vivo evaluation of [18F]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide as a PET imaging probe for COX-2 expression

Synthesis of [F-18]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ([F-18]celecoxib), a selective COX-2 inhibitor, is achieved via a bromide to [F-18]F- exchange reaction. Synthesis of the precursor for radiolabeling was achieved from 4'-methylacetophenone in four steps with 22% overall yield. Under non-radioactive conditions, fluorination was achieved using TBAF in DMSO at 135 degrees C in 80% yield. Synthesis of [F-18]celecoxib was achieved using [F-18]TBAF in DMSO at 135 degrees C in 10 +/- 2% yield (EOS) with > 99% chemical and radiochemical purities. The specific activity was 120 +/- 40 mCi/mu mol (EOB). [F-18]celecoxib was found to be stable in ethanol, however, de[F-18]fluorination (6.5%) was observed after 4 h in 10% ethanol-saline solution. Rodent PET studies show bone labeling indicating in vivo de[F-18]fluorination of [F-18]celecoxib. PET studies in baboon indicated a lower rate of de[F-18]fluorination than rat and retention of radioactivity in brain regions consistent with the known distribution of COX-2. A radiolabeling method that can generate consistent high specific activity is needed for routine human use. (c) 2006 Elsevier Ltd. All rights reserved.