Positron emission tomography imaging of D(2/3) agonist binding in healthy human subjects with the radiotracer [(11)C]-N-propyl-norapomorphine: preliminary evaluation and reproducibility studies.

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 (<or=10%) in all regions, for this approach. The reproducibility of both BP(P) (<or=12%) and BP(ND) (<or=10%) was also excellent. The intraclass correlation coefficients of BP(P) and BP(ND) were acceptable as well (>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.