KINETIC MODELLING OF NICOTINIC ACETYLCHOLINE RECEPTORS WITH 5-~(123)IIODO-A-85380 AND DYNAMIC SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY

摘要

5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-[~(123)I]iodo-A-85380) is a novel ra-dioligand for brain nicotinic acetylcholine receptors (nAChRs), having demonstrated high specific binding to nAChRs and favourable properties for in vivo imaging. The purpose of this study was to evaluate different tracer kinetic modelling strategies for the quantification of regional nAChR binding in baboon brain using dynamic single-photon emission computed tomography (SPECT). Imaging studies were performed on two anaesthetised baboons. The radioligand (397+-43 MBq) was infused into the animals over 2 min and dynamic SPECT images were acquired for 3 hr. The plasma input function was determined from arterial blood samples with metabolite correction. The data were analysed using 2- and 3-compartment models. Reliable fits could be obtained with a 3-compartment model which provided significantly improved fitting as compared to the 2-compartment model, despite poor identifiability in some parameters. The 2-compartment model failed to fit the data adequately even though the identifiability of parameters was high. The 3-compartment model described the data well, and with the strategies used to obtain reliable fits, is the model of choice for analysis of 5-[~(123)I]iodo-A-85380 kinetics.