PET studies of peripheral catechol-O-methyltransferase in non-human primates using [F-18]Ro41-0960

We previously reported the results of PET (positron emission tomography) st udies of [F-18]Ro41-0960, a potent COMT inhibitor, in baboon brain. Here we report an evaluation of the pharmacokinetics and specificity of binding of [F-18]Ro41-0960 in the peripheral organs of baboon. We observed a rapid cl earance of the tracer from the heart and no significant uptake in the lung. In contrast, there was a high uptake and slow clearance in both kidney and liver, consistent with a high level of COMT in these peripheral organs. We also observed a dose-dependent inhibition of [F-18]Ro41-0960 uptake by unl abeled Ro41-0960 (ED,, was 0.5mg/kg in liver, and <0.01 mg/kg in kidney), w ith a half time for recovery of COMT of about 25 h at the dose of 2 mg/kg o f unlabeled Ro41-0960. This indicates a reversible tight binding interactio n between COMT and Ro41-0960 in both liver and kidney and suggests that [F- 18]Ro41-0960 may be a useful radiotracer for future examination of the func tional activity of COMT in the human body.