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
Version of Record online: 19 MAR 2009
Copyright © 2009 Wiley-Liss, Inc.
Volume 63, Issue 7, pages 574–584, July 2009
How to Cite
Narendran, R., Frankle, W. G., Mason, N. S., Laymon, C. M., Lopresti, B. J., Price, J. C., Kendro, S., Vora, S., Litschge, M., Mountz, J. M. and Mathis, C. A. (2009), 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. Synapse, 63: 574–584. doi: 10.1002/syn.20633
- Issue online: 19 MAR 2009
- Version of Record online: 19 MAR 2009
- Manuscript Accepted: 25 OCT 2008
- Manuscript Received: 21 AUG 2008
- NIMH (Career Development Award). Grant Number: 1-K08 MH 068762-03
- Department of Radiology, University of Pittsburgh
- D2/3 agonist
(−)-N-[11C]-propyl-norapomorphine (NPA) is a full dopamine D2/3 receptor agonist radiotracer suitable for imaging D2/3 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 D2/3 receptor parameters with [11C]NPA.
Six healthy subjects (four females/two males) underwent two [11C]NPA scans in the same day. D2/3 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 (VT), binding potential relative to plasma concentration (BPP), and binding potential relative to nondisplaceable uptake (BPND).
A two-tissue compartment kinetic model adequately described the functional subdivisions of the striatum as well as cerebellum time-activity data. The reproducibility of VT 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 (r2 = 0.89, n = 84). Both methods were similarly effective in detecting the differences in [11C]NPA BPND between subjects.
The results of this study indicate that [11C]NPA can be used to measure D2/3 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. © 2009 Wiley-Liss, Inc.