QUANTIFICATION OF 5-~(123)IIODO-A-85380 IN NONHUMAN PRIMATES USING SPECT: PARAMETER IDENTIFIABILITY AND STABILITY

摘要

5-[~(123)I]iodo-A-85380, namely 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine, is a new, highly selective radioligand with favourable properties for in vivo imaging of neuronal nicotinic acetylcholine receptors (nAChRs) using single-photon emission computed tomography (SPECT). The aim of this work was to study the identifiability and stability of nAChR parameters in baboon brain using different tracer kinetic modelling strategies with shortened scan durations. Dynamic SPECT imaging studies were performed on two anaesthetised baboons for 3 hours. Kinetic analysis based on 2- and 3-compartment models was used to derive the receptor parameters, including the binding potential (BP) and the volume of distribution (V_d), using the arterial plasma time-activity curves as the input function. Based on the 3-compartment model, V_d was selected as an appropriate outcome measure to assess the parameter stability due to high variability in estimation of BP. Time-stability analysis indicated that 90 mins of data collection generated stable outcome measure for 3-compartment model and the use of the 2-compartment model produced outcome measure with a larger bias. Thus, the 3-compartment model is the model of choice for analysis of 5-[~(123)I]iodo-A-85380 kinetics and the 2-compartment model is useful only when the data acquisition time is sufficiently long.