Positron emission tomography (PET) with 11 Craclopride has been used to investigate the density (Bmax) and affinity (Kd) of dopamine D2 receptors related to several neurological and psychiatric disorders. However, in assessing the Bmax and Kd, 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 Bmax and Kd 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 Bmax and K d estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of B max and Kd, despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the Bmax and Kd of diseased or normal striatum in a 150 mins scan with the three-injection protocol of 11 Craclopride. Estimated Bmax and K d values of D2 receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values.
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