Positron Emission Tomography Imaging of D2/3 Agonist Binding in Healthy Human Subjects With the Radiotracer [11C]-N-Propyl-Norapomorphine: Preliminary Evaluation and Reproducibility Studies

Objective: (-)-N-[C-11]-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 [C-11]NPA. Methods: Six healthy subjects (four females/two males) underwent two [C-11]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 (BPP), and binding potential relative to nondisplaceable uptake (BPND). 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 (<= 10%) in all regions, for this approach. The reproducibility of both BPP (<= 12%) and BPND (<= 10%) was also excellent. The intraclass correlation coefficients of BPP and BPND were acceptable as well (>0.75) in the three functional subdivisions of the striatum. Although SRTM led to an underestimation of BPND 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 [C-11]NPA BPND between subjects. Conclusion: The results of this study indicate that [C-11]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. Synapse 63:574-584, 2009. (C) 2009 Wiley-Liss, Inc.