Abstract
Positron emission tomography (PET) with [(11)C]raclopride has been used to investigate the density (B(max)) and affinity (K(d)) of dopamine D(2) 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)C]raclopride, 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)C]raclopride, 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)C]raclopride. Estimated B(max) and K(d) values of D(2) receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values.