Synthesis and evaluation in vitro and in vivo of a ¹¹C-labeled cyclooxygenase-2 (COX-2) inhibitor

The radiosynthesis and radiopharmacological evaluation of 1-[¹¹C]methoxy-4-(2-(4-(methanesulfonyl) phenyl)cyclopent-1-enyl)-benzene [¹¹C]5 as novel PET radiotracer for imaging of COX-2 expression is described\. The radiotracer was prepared via O-methylation reaction with [¹¹C]methyl iodide in 19% decay-corrected radiochemical yield at a specific activity of 20–25 GBq/lmol at the end-of-synthesis within 35 min. The radiotracer [¹¹C]5 was evaluated in vitro using various pro-inflammatory and tumor cell lines showing high functional expression of COX-2 at baseline or after induction. In vivo biodistribution of compound [¹¹C]5 was characterized in male Wistar rats. Compound [¹¹C]5 was rapidly metabolized in rat plasma, and more pronounced, in mouse plasma. In vivo kinetics and tumor uptake were demonstrated by dynamic small animal PET studies in a mouse tumor xenograft model. Tumor uptake of radioactivity was clearly visible overtime. However, radioactivity uptake in the tumor could not be blocked by the pre-injection of nonradioactive compound 5. Therefore, it can be concluded that radioactivity uptake in the tumor was not COX-2 mediated.