Effect of tracer metabolism on PET measurement of [C-11]pyrilamine bindingto histamine H-1 receptors

The present study was carried out to investigate the time course of [C-11]p yrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [C-11]pyrilamine and its labeled metabolites were determ ined. After intravenous injection, [C-11]pyrilamine metabolized gradually i n the human body, with less than 10% of plasma activity being original radi oligand at 60 min. Tracer metabolism markedly affected the input function a nd the calculated impulse response function of the brain. Rat experiments d emonstrated that although metabolites of [C-11]pyrilamine might enter the b rain, they were not retained for prolonged periods of time. At 30-90 min af ter injection of [C-11]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [C-11]pyrilamine. Based on the r at data, the contribution of C-11-labeled metabolites to total [C-11]pyrila mine radioactivity in the human brain was estimated and found to be negligi ble. These results suggest that the metabolites of [C-11]pyrilamine do not accumulate within the cerebral extravascular space and that there is minima l metabolism of [C-11]pyrilamine by brain tissue itself. Therefore, [C-11]p yrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [C-11]pyrilamine binding to histamine H-1 receptors.