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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 [(11)C]raclopride, a dopamine D(2) receptor (D(2)R) ligand, and cold raclopride (10 and 100 μg/kg) in the brains of conscious monkeys. The present results demonstrated that the FC-B/I method could achieve the equilibrium state of [(11)C]raclopride in the striatum of monkey brain, and also that the cold raclopride-induced reduction of [(11)C]raclopride binding to D(2)R 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.

Feedback-Controlled Bolus plus Infusion (FC-B/I) Method for Quantitative Drug Assessment in Living Brain with PET