Evaluation of Two Potent and Selective PET Radioligands to Image COX-1 and COX-2 in Rhesus Monkeys.

Abstract

This study assessed whether the newly developed PET radioligands ¹¹C-PS13 and ¹¹C-MC1 could image constitutive levels of cyclooxygenase (COX)-1 and COX-2, respectively, in rhesus monkeys. <b>Methods:</b> After intravenous injection of either radioligand, 24 whole-body PET scans were performed. To measure enzyme-specific uptake, scans of the 2 radioligands were also performed after administration of a nonradioactive drug preferential for either COX-1 or COX-2. Concurrent venous samples were obtained to measure parent radioligand concentrations. SUVs were calculated from 10 to 90 min. <b>Results:</b>¹¹C-PS13 showed specific uptake in most organs, including spleen, gastrointestinal tract, kidneys, and brain, which was blocked by COX-1, but not COX-2, preferential inhibitors. Specific uptake of ¹¹C-MC1 was not observed in any organ except the ovaries and possibly kidneys. <b>Conclusion:</b> The findings suggest that ¹¹C-PS13 has adequate signal in monkeys to justify its extension to human subjects. In contrast, ¹¹C-MC1 is unlikely to show significant signal in healthy humans, though it may be able to do so in inflammatory conditions.