Efficient sequential synthesis of PET Probes of the COX-2 inhibitor [11C]celecoxib and its major metabolite [11C]SC-62807 and in vivo PET evaluation

Synthesis of (11)C]celecoxib, a selective COX-2 inhibitor, and (11)C]SC-62807, a major metabolite of celecoxib, were achieved and the potential of these PET probes for assessing the function of drug transporter in biliary excretion was evaluated. The synthesis of (11)C]celecoxib was achieved in one-pot by reacting (11)C]methyl iodide with an excess of the corresponding pinacol borate precursor using Pd(2)(dba)(3), P(o-tolyl)(3), and K(2)CO(3) (1:4:9) in DMF. The radiochemical yield of (11)C]celecoxib was 63±23% (decay-corrected, based on (11)C]CH(3)I) (n=7) with a specific radioactivity of 83±23GBq/μmol (n=7). The average time of synthesis from end of bombardment including formulation was 30min with >99% radiochemical purity. (11)C]SC-62807 was synthesized from (11)C]celecoxib by further rapid oxidation in the presence of excess KMnO(4) with microwave irradiation. The radiochemical yield of (11)C]SC-62807 was 55±9% (n=3) (decay-corrected, based on (11)C]celecoxib) with a specific radioactivity of 39±4GBq/μmol (n=3). The average time of synthesis from (11)C]celecoxib including formulation was 20min and the radiochemical purity was >99%. PET studies in rats and the metabolite analyzes of (11)C]celecoxib and (11)C]SC-62807 showed largely different excretion processes, and consequently, (11)C]SC-62807 was rapidly excreted via hepatobiliary excretion without further metabolism. (11)C]SC-62807 was shown to have a high potential as a PET probe for evaluating drug transporter function in biliary excretion.