IN-VIVO SATURATION KINETICS OF 2 DOPAMINE TRANSPORTER PROBES MEASUREDUSING A SMALL ANIMAL POSITRON-EMISSION-TOMOGRAPHY SCANNER

When estimated in vitro, the parameters which describe the binding of radiolabelled analogues of cocaine to sites on the dopamine transporte r are very much influenced by the methodology used. In the present stu dy, a small animal positron emission tomography (PET) scanner was used to estimate in vivo saturation kinetics for two carbon-11 labelled co mpounds presently used to monitor dopamine terminal function. The bind ing of [C-11]CFT (WIN 35,428) in rat striatum was adequately described by a single-site model, giving an apparent dissociation constant corr esponding to an intravenous dose of 242 nmol/kg. In contrast, the bind ing of [C-11]RTI-121 was better described by a two-site model with the 'high-affinity' site or state (dissociation constant = 1 nmol/kg) bei ng significantly occupied at doses routinely used in PET scanning. Suc h findings cannot readily be predicted from in vitro work, but could a id in both the choice of ligand and the model used in quantification o f scan data. While multi-dose in vivo PET studies are difficult in man , rat PET can easily be employed either pre-clinically for putative ra dioligands, or experimentally, to study drug interactions and receptor occupancy related to functional efficacy. (C) 1997 Elsevier Science B .V.