Measurement of density and affinity for dopamine D 2 receptors by a single positron emission tomography scan with multiple injections of 11 Craclopride

Positron emission tomography (PET) with 11 Craclopride has been used to investigate the density (B_max) and affinity (K_d) of dopamine D₂ receptors related to several neurological and psychiatric disorders. However, in assessing the B_max and K_d, multiple PET scans are necessary under variable specific activities of administered 11 Craclopride, resulting in a long study period and unexpected physiological variations. In this paper, we have developed a method of multiple-injection graphical analysis (MI-GA) that provides the B_max and K_d values from a single PET scan with three sequential injections of 11 Craclopride, and we validated the proposed method by performing numerous simulations and PET studies on monkeys. In the simulations, the three-injection protocol was designed according to prior knowledge of the receptor kinetics, and the errors of B_max and K d estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of B _max and K_d, despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the B_max and K_d of diseased or normal striatum in a 150 mins scan with the three-injection protocol of 11 Craclopride. Estimated B_max and K _d values of D₂ receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values.