In vivo DA D(1) receptor selectivity of NNC 112 and SCH 23390.
OBJECTIVE
[(11)C]NNC 112 and [(11)C]SCH 23390 are selective positron emission tomography (PET) tracers for visualizing dopamine D(1) receptors. It is known that both have some affinity for serotonin 2A receptors, but previous studies have suggested this is negligible compared to D(1) affinity. We sought to verify this property in vivo.


METHODS
Two baboons were scanned to measure the selectivity of both tracers with a displacement paradigm. Four baboons were scanned to directly assess [(11)C] NNC 112 affinity for both receptors.


RESULTS
In vivo, D(1) to 5-HT(2A) selectivity is six to fourteenfold, not 100-fold as previously reported by other investigators.


CONCLUSIONS
We conclude that about 1/4 of the cortical signal of both [(11)C]NNC 112 and [(11)C]SCH 23390 is due to binding to 5-HT(2A) receptors. If confirmed in humans, this suggests caution should be exercised when drawing conclusions from studies using either tracer. These results also indicate the need for more selective tracers for the D(1) receptor.
Ekelund
Jesper
J
Department of Psychiatry, Columbia University, New York, NY, USA.
Slifstein
Mark
M
Narendran
Raj
R
Guillin
Olivier
O
Belani
Hemant
H
Guo
Ning-Ning
NN
Hwang
Yuying
Y
Hwang
Dah-Ren
DR
Abi-Dargham
Anissa
A
Laruelle
Marc
M
D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics*; D001572:Benzofurans / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
D001552:Benzazepines; D001572:Benzofurans; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; D017447:Receptors, Dopamine D1; C077123:NNC 112