SPECT imaging with the D4 receptor antagonist L-750,667 in nonhuman primate brain

The suitability of an 123I-labeled form of the putative D4 receptor ligand L750,667 as a radiotracer for single photon emission computed tomography imaging was assessed in nonhuman primates. [123I]L750,667, labeled by iododestannylation, was administered to baboons in bolus and bolus plus constant infusion paradigms and imaged for 6 h. Total [123I]L750,667 brain uptake peaked (2.3% injected dose) at 15 min postinjection. [123I]L750,667 uptake was observed in all brain regions measured including diencephalon, brainstem, basal ganglia, cingulate cortex, and cerebellum, and slightly lower levels were noted in the frontal, parietal, temporoinsular, and occipital cortices. Administration of the D4 receptor antagonist NGD 94-1 (2 mg/kg) did not displace radioactivity from any of the brain regions examined. Thus, while L750,667 is selective for the D4 receptor in vitro, because brain [123I]L750,667 uptake was not displaced by NGD 94-1 at receptor saturating doses, [123I]L750,667 does not appear to be a suitable radiotracer for in vivo imaging of the D4 receptor