Abstract
OBJECTIVE: (-)-N-[(11)C]-propyl-norapomorphine (NPA) is a full dopamine D(2/3) receptor agonist radiotracer suitable for imaging D(2/3) receptors configured in a state of high affinity for agonists using positron emission tomography. The aim of the present study was to define the optimal analytic method to derive accurate and reliable D(2/3) receptor parameters with [(11)C]NPA. METHODS: Six healthy subjects (four females/two males) underwent two [(11)C]NPA scans in the same day. D(2/3) receptor-binding parameters were estimated using kinetic analysis (using one- and two-tissue compartment models) as well as simplified reference tissue method in the three functional subdivisions of the striatum (associative striatum, limbic striatum, and sensorimotor striatum). The test-retest variability and intraclass correlation coefficient were assessed for distribution volume (V(T)), binding potential relative to plasma concentration (BP(P)), and binding potential relative to nondisplaceable uptake (BP(ND)). RESULTS: A two-tissue compartment kinetic model adequately described the functional subdivisions of the striatum as well as cerebellum time-activity data. The reproducibility of V(T) was excellent (0.75) in the three functional subdivisions of the striatum. Although SRTM led to an underestimation of BP(ND) values relative to that estimated by kinetic analysis by 8-13%, the values derived using both the methods were reasonably well correlated (r(2) = 0.89, n = 84). Both methods were similarly effective in detecting the differences in [(11)C]NPA BP(ND) between subjects. CONCLUSION: The results of this study indicate that [(11)C]NPA can be used to measure D(2/3) receptors configured in a state of high affinity for the agonists with high reliability and reproducibility in the functional subdivisions of the human striatum.