Cerebral uptake of [ethyl-11C]vinpocetine and 1-[11C]ethanol in cynomolgous monkeys: a comparative preclinical PET study.

PET provides the potential to quantify the distribution of radiolabelled drugs in the human body. In cases when radiolabelled compounds undergo metabolic transformation after administration in vivo, it is necessary to examine the kinetics and distribution of both the labeled mother compound and labeled metabolites. The objective of this study was to assess the extent by which 11C-labeled ethanol, the product arising from the de-esterification of the neuroprotective drug vinpocetine (ethyl-apovincaminate), might contribute to the regional cerebral radioactivity measured by PET after the administration of [ethyl-11C]vinpocetine. In three cynomolgous monkeys PET measurements were made after intravenous bolus injection of both [11C]vinpocetine and 1-[11C]ethanol. There was a marked difference between the regional time-activity curves of [11C]ethanol and [11C]vinpocetine. The distribution pattern obtained with [11C]ethanol was similar to that observed with blood flow tracers such as [15O]water and [15O]butanol. The study shows that although [11C]ethanol may moderately contribute to the brain radioactivity distribution pattern of [11C]vinpocetine, the rapid degradation of [11C]ethanol makes it unlikely that the contribution of this metabolite is of importance. The distinct distribution patterns and kinetics of [11C]vinpocetine and [11C]ethanol also support the view, obtained from our previous observations, that vinpocetine may bind to specific sites in the monkey and human brain, especially in the thalamus.