Graphical, Kinetic, and Equilibrium Analyses of in vivo [123I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects

Abstract

The in vivo kinetics of the dopamine (DA) transporter probe 123I-labeled 2β-carboxymethoxy-3β-(4-iodophenyl)tropane ([123I]β-CIT) in striatum was investigated with single-photon emission computerized tomography (SPECT) in five healthy human subjects. The aim of this study was to derive an adequate measure of the DA transporter density that would not be affected by regional cerebral blood flow or peripheral clearance of the tracer. SPECT data were acquired on the day of injection (day 1) from 0 to 7 h and on the following day (day 2) from 19 to 25 h. Arterial sampling on day 1 was used to measure the input function. Graphical, kinetic, and equilibrium analyses were evaluated. Graphical analysis of day 1 data, with the assumption of negligible dissociation of the tracer–receptor complex ( k4 = 0), was found to be blood flow-dependent. A three-compartment kinetic analysis of day 1 data were performed using a three ( k4 = 0)- and a four ( k4 > 0)-parameter model. The three-parameter model estimated the kon Bmax product at 0.886 ± 0.087 min−1. The four-parameter model gave a binding potential (BP) of 476 ml g−1, a value consistent with in vitro measurements. The stability of the regional uptake on day 2 allowed direct measurement of the specific to nonspecific equilibrium partition coefficient (V3″ = k3/ k4 = 6.66 ± 1.54). Results of day 1 kinetic analysis and day 2 equilibrium analysis were well correlated among subjects. Simulations indicated that the error associated with the day 2 equilibrium analysis was acceptable for plasma tracer terminal half-lives >10 h. We propose the equilibrium analysis on day 2 as the method of choice for clinical studies since it does not require multiple scans or the measurement of the arterial plasma tracer concentrations.