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.


CONCLUSIONS
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.
Narendran
Rajesh
R
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. narendranr@upmc.edu
Frankle
W Gordon
WG
Mason
N Scott
NS
Laymon
Charles M
CM
Lopresti
Brian J
BJ
Price
Julie C
JC
Kendro
Steve
S
Vora
Shivangi
S
Litschge
Maralee
M
Mountz
James M
JM
Mathis
Chester A
CA
D000328:Adult; D000704:Analysis of Variance; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000009:adverse effects / Q000097:blood; D049268:Positron-Emission Tomography / Q000379:methods*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D015203:Reproducibility of Results; D013997:Time Factors; D055815:Young Adult
D002250:Carbon Radioisotopes; D009019:Morphinans; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C089092:N-propyl-noroxymorphone