SPECT imaging with the D(4) receptor antagonist L-750,667 in nonhuman primate brain.
The suitability of an (123)I-labeled form of the putative D(4) receptor ligand L750,667 as a radiotracer for single photon emission computed tomography imaging was assessed in nonhuman primates. [(123)I]L750,667, labeled by iododestannylation, was administered to baboons in bolus and bolus plus constant infusion paradigms and imaged for 6 h. Total [(123)I]L750,667 brain uptake peaked (2.3% injected dose) at 15 min postinjection. [(123)I]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 D(4) 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 D(4) receptor in vitro, because brain [(123)I]L750,667 uptake was not displaced by NGD 94-1 at receptor saturating doses, [(123)I]L750,667 does not appear to be a suitable radiotracer for in vivo imaging of the D(4) receptor.
Staley
J K
JK
Department of Psychiatry, Yale University School of Medicine & VA Connecticut Healthcare System, West Haven, Connecticut, USA. julie.staley@yale.edu
Tamagnan
G
G
Baldwin
R M
RM
Fujita
M
M
Al Tikriti
M S
MS
Eshima
L
L
Thornback
J
J
Roe
D
D
Lu
L
L
Seibyl
J P
JP
Innis
R B
RB
D000818:Animals; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D065127:Dopamine D2 Receptor Antagonists; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007457:Iodine Radioisotopes; D009778:Occipital Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D009928:Organ Specificity; D010215:Papio; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000097:blood / Q000493:pharmacokinetics*; D050638:Receptors, Dopamine D4; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007093:Imidazoles; D007457:Iodine Radioisotopes; C103081:L 750667; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D050638:Receptors, Dopamine D4; C107692:NGD 94-1