title: Feedback-controlled bolus plus infusion (FC-B/I) method for quantitative drug assessment in living brain with PET.
abstract: 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.
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics KK, Hamamatsu, Japan. h-ohba@crl.hpk.co.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohba
authors.forename: Norihiro
authors.initials: N
authors.lastname: Harada
authors.forename: Shingo
authors.initials: S
authors.lastname: Nishiyama
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kakiuchi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005246:Feedback; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D020891:Raclopride / Q000008:administration & dosage / Q000494:pharmacology; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D018492:Dopamine Antagonists; D008024:Ligands; D017448:Receptors, Dopamine D2; D020891:Raclopride