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 [¹⁸F]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ([¹⁸F]celecoxib), a selective COX-2 inhibitor, is achieved via a bromide to [¹⁸F]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 °C in 80% yield. Synthesis of [¹⁸F]celecoxib was achieved using [¹⁸F]TBAF in DMSO at 135 °C in 10 ± 2% yield (EOS) with >99% chemical and radiochemical purities. The specific activity was 120 ± 40 mCi/μmol (EOB). [¹⁸F]celecoxib was found to be stable in ethanol, however, de[¹⁸F]fluorination (6.5%) was observed after 4 h in 10% ethanol-saline solution. Rodent PET studies show bone labeling indicating in vivo de[¹⁸F]fluorination of [¹⁸F]celecoxib. PET studies in baboon indicated a lower rate of de[¹⁸F]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.