Feedback-controlled bolus plus infusion (FC-B/I) method for quantitative drug assessment in living brain with PET

We have developed a feedback-controlled bolus plus infusion (FC-B/I) method for monitoring the interaction between positron emission tomography (PET) ligands and their specific target molecules with PET. The usefulness of the FC-B/I method was evaluated by the direct interaction between [C-11]raclopride, a dopamine D-2 receptor (D2R) ligand, and cold raclopride (10 and 100 mu g/kg) in the brains of conscious monkeys. The present results demonstrated that the FC-B/I method could achieve the equilibrium state of [C-11]raclopride in the striatum of monkey brain, and also that the cold raclopride-induced reduction of [C-11]raclopride binding to D2R was observed in a dose-dependent manner. Good correlations of distribution volume ratio of the striatum to cerebellum between the conventional bolus plus infusion (B/I) method and the FC-B/I method as well as between the conventional bolus injection method and the FC-B/I method were observed. These results indicated that the system could be a useful tool for the evaluation of interaction between drug candidates and their target molecules like enzymes, receptors, and transporters by using of their specific PET ligands. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 85-90; doi:10.1038/jcbfm.2012.134; published online 12 September 2012