Measurement of density and affinity for dopamine D sub(2) receptors by a single positron emission tomography scan with multiple injections of [ super(11)C]raclopride

Positron emission tomography (PET) with [ super(11)C]raclopride has been used to investigate the density (B sub(max)) and affinity (K sub(d)) of dopamine D sub(2) receptors related to several neurological and psychiatric disorders. However, in assessing the B sub(max) and K sub(d), multiple PET scans are necessary under variable specific activities of administered [ super(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 sub(max) and K sub(d) values from a single PET scan with three sequential injections of [ super(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 sub(max) and K sub(d) estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of B sub(max) and K sub(d), despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the B sub(max) and K sub(d) of diseased or normal striatum in a 150mins scan with the three-injection protocol of [ super(11)C]raclopride. Estimated B sub(max) and K sub(d) values of D sub(2) receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values.