Measurement of density and affinity for dopamine D-2 receptors by a single positron emission tomography scan with multiple injections of [C-11]raclopride
: Ikoma Y, Watabe H, Hayashi T, Miyake Y, Teramoto N, Minato K, Iida H
Publisher: NATURE PUBLISHING GROUP
: 2010
: Journal of Cerebral Blood Flow and Metabolism
: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
: J CEREBR BLOOD F MET
: 30
: 3
: 663
: 673
: 11
: 0271-678X
DOI: https://doi.org/10.1038/jcbfm.2009.239
Positron emission tomography (PET) with [C-11]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 [C-11]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 [C-11]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 [C-11]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. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 663-673; doi: 10.1038/jcbfm.2009.239; published online 11 November 2009