Kinetic Modeling of Receptor‐Ligand Binding Applied to Positron Emission Tomographic Studies with Neuroleptic Tracers

Abstract: Positron emission tomography (PET) with labeled neuroleptics has made possible the study of neurotransmitter‐receptor systems in vivo. In this study we investigate the kinetics of the 3, 4‐dihydroxyphenylethylamine (dopamine) receptor‐ligand binding using PET data from a series of experiments in the baboon with the ¹⁸F‐labeled drugs spiperone, haloperidol, and benperidol. Models used to describe these systems are based on first‐order kinetics which applies at high specific activity (low receptor occupancy). The parameters governing the uptake and loss of drug from the brain were found by fitting PET data from regions with little or no receptor concentration (cerebellum) and from experiments in which specific binding was blocked by pretreatment with the drug (+)‐butaclamol. Receptor constants were determined by fitting data from receptor‐containing structures. Correcting the arterial plasma activities (the model driving function) for the presence of drug metabolites was found to be important in the modeling of these systems.