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

We previously reported the results of PET (positron emission tomography) studies of [¹⁸F]Ro41-0960, a potent COMT inhibitor, in baboon brain. Here we report an evaluation of the pharmacokinetics and specificity of binding of [¹⁸F]Ro41-0960 in the peripheral organs of baboon. We observed a rapid clearance 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 [¹⁸F]Ro41-0960 uptake by unlabeled Ro41-0960 (ED₅₀ was O.5 mg/kg in liver, and < 0.01 mg/kg in kidney), with a halftime for recovery of COMT of about 25 h at the dose of 2 mg/kg of unlabeled Ro41-0960. This indicates a reversible tight binding interaction between COMT and Ro41-0960 in both liver and kidney and suggests that [¹⁸F]Ro41-0960 may be a useful radiotracer for future examination of the functional activity of COMT in the human body.