Quantification of Neuroreceptors and Neurotransporters

Abstract

The binding potential relative to the concentration of nondisplaceable radiotracer in brain (BP_ND), corresponding to the ratio of the density of neuroreceptors or neurotransporters available to bind radiotracer in vivo (B _avail) to the dissociation constant of the radiotracer (K _D), can be measured by positron emission tomography (PET) with various radiotracers. PET measures the total radioactivity in brain regions, and therefore the differentiation of specific binding from the background of nondisplaceable binding is a fundamental problem in quantitative analyses of PET data. A true equilibrium condition can be obtained only by continuous intravenous infusion of radiotracer. Equilibrium condition after bolus injection of radiotracer can practically be defined as peak equilibrium at the transient moment when the specific binding is maximal. For equilibrium condition, BP_ND is expressed as the ratio of radiotracer concentration of specific binding to nondisplaceable binding estimated using a reference region. Kinetic analysis, which is based on the assumption that radiotracer binding can be described by the standard two-tissue compartment model, allows the differentiation of the specific binding from the background of nondisplaceable binding, therefore revealing BP_ND. For radiotracers with no ideal reference region, BP_ND can be calculated only by kinetic analysis. Distribution volumes can also be estimated by several graphic plot analyses, as well as by kinetic analysis. Graphic plot analyses can be used to distinguish graphically whether radiotracers show reversible or irreversible binding. A graphic plot analysis recently developed can also be used to distinguish graphically whether the radiotracer binding includes specific binding or not. To avoid the measurement of arterial input function, several quantitative approaches based on the use of a reference region have been developed. Both the simplified reference tissue model and multilinear reference tissue model methods were widely used to calculate BP_ND without the arterial input function. For each radiotracer and each purpose of PET study, an adequate quantification method should be employed.