SPECT imaging with the D-4 receptor antagonist L-750,667 in nonhuman primate brain

The suitability of an I-123-labeled form of the putative D-4 receptor ligan d L750,667 as a radiotracer for single photon emission computed tomography imaging was assessed in nonhuman primates. [I-123]L750,667, labeled by iodo destannylation, was administered to baboons in bolus and bolus plus constan t infusion paradigms and imaged for 6 h. Total [I-123]L750,667 brain uptake peaked (2.3% injected dose) at 15 min postinjection. [I-123]L750,667 uptak e was observed in all brain regions measured including diencephalon, brains tem, basal ganglia, cingulate cortex, and cerebellum, and slightly lower le vels were noted in the frontal, parietal, temporoinsular, and occipital cor tices. Administration of the D-4 receptor antagonist NGD 94-1 (2 mg/kg) did not displace radioactivity from any of the brain regions examined. Thus, w hile L750,667 is selective for the D-4 receptor in vitro, because brain [I- 123]L750,667 uptake was not displaced by NGD 94-1 at receptor saturating do ses, [I-123]L750,667 does not appear to be a suitable radiotracer for in vi vo imaging of the D-4 receptor. NUCL MED BIOL 27;6:5411-556, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.