A new graphic plot analysis for determination of neuroreceptor binding in positron emission tomography studies

In positron emission tomography (PET) studies with radioligands for neuroreceptors, tracer kinetics have been described by the standard two-tissue compartment model that includes the compartments of nondisplaceable binding and specific binding to receptors. In the present study, we have developed a new graphic plot analysis to determine the total distribution volume (V_T) and nondisplaceable distribution volume (V_ND) independently, and therefore the binding potential (BP_ND). In this plot, Y(t) is the ratio of brain tissue activity to time-integrated arterial input function, and X(t) is the ratio of time-integrated brain tissue activity to time-integrated arterial input function. The x-intercept of linear regression of the plots for early phase represents V_ND, and the x-intercept of linear regression of the plots for delayed phase after the equilibrium time represents V_T. BP_ND can be calculated by BP_ND = V_T / V_ND - 1. Dynamic PET scanning with measurement of arterial input function was performed on six healthy men after intravenous rapid bolus injection of [¹¹C]FLB457. The plot yielded a curve in regions with specific binding while it yielded a straight line through all plot data in regions with no specific binding. V_ND, V_T, and BP_ND values calculated by the present method were in good agreement with those by conventional non-linear least-squares fitting procedure. This method can be used to distinguish graphically whether the radioligand binding includes specific binding or not.