ABSTRACT
In conventional pharmacological research in the field of mental disorders, pharmacological effect and dose have been estimated by ethological approach and in vitro data of affinity to the site of action. In addition, the frequency of administration has been estimated from drug kinetics in blood. However, there is a problem regarding an objective index of drug effects in the living body. Furthermore, the possibility that the concentration of drug in blood does not necessarily reflect the drug kinetics in target organs has been pointed out. Positron emission tomography (PET) techniques have made progress for more than 20 years, and made it possible to measure the distribution and kinetics of small molecule components in living brain. In this article, we focused on rational drug dosing using receptor occupancy and proof-of-concept of drugs in the drug development process using PET.
Subject(s)
Brain , Central Nervous System , Drug Evaluation , Electrons , Kinetics , Mental Disorders , Norepinephrine Plasma Membrane Transport Proteins , Positron-Emission Tomography , Receptors, Dopamine D2 , Serotonin Plasma Membrane Transport ProteinsABSTRACT
Manual drawing of regions of interest (ROIs) on brain positron emission tomography (PET) images is labour intensive and subject to intra- and inter-individual variations. To standardize analysis and improve the reproducibility of PET measures, we have developed image analysis software for automated quantification of PET data. The method is based on the individualization of a set of standard ROIs using a magnetic resonance (MR) image co-registered with the PET image. To evaluate the performance of this automated method, the software-based quantification has been compared with conventional manual quantification of PET images obtained using three different PET radiotracers: [(11)C]-WAY 100635, [(11)C]-raclopride and [(11)C]-DASB. Our results show that binding potential estimates obtained using the automated method correlate highly with those obtained by trained raters using manual delineation of ROIs for frontal and temporal cortex, thalamus, and striatum (global intraclass correlation coefficient >0.8). For the three radioligands, the software yields time-activity data that are similar (within 8%) to those obtained by manual quantification, eliminates investigator-dependent variability, considerably shortens the time required for analysis and thus provides an alternative method for accurate quantification of PET data.
