TY - JOUR
T1 - [11C]A-69024
T2 - A potent and selective non-benzazepine radiotracer for in vivo studies of dopamine D1 receptors
AU - Kassiou, Michael
AU - Scheffel, Ursula
AU - Ravert, Hayden T.
AU - Mathews, William B.
AU - Musachio, John L.
AU - Lambrecht, Richard M.
AU - Dannals, Robert F.
N1 - Funding Information:
Acknowledgements-Thea uthors would like to thank Mr Paige Finley for her skilful assistancwe ith in ciuoa nimal experimentsa, nd Mr Robert Smoot for his help with the radiosynthesesW. e would also like to thank Dr Daniel Kerkman of Abbot Pharmaceuticalfso r his generousg ift of authenticA -69024.T his work was supportedin part by the U.S. Public Health ServiceG rants: NS 15080,C A-09199, and CA 32845,a nd the DOE DE-FGO2-~ER61~6.
PY - 1995/2
Y1 - 1995/2
N2 - [11C]A-69024, (±)-1-(2-bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-2-[1 1C]methyl-1,2,3,4-tetra-hydroisoquinoline, is a specific and selective dopamine D1 radiotracer. The in vivo biodistribution of this novel radioligand in mice showed a high uptake in the striatum (6.7%ID/g) at 5 min, followed by clearance with a half-life of 16.1 min. As a measure of specificity, the striatal/cerebellar ratio reached a maximum of 7.4 at 30 min post-injection. Radioactivity in the striatum was reduced to the level of the cerebellum by pre-adminstration of the D1 antagonist SCH 23390 (1 mg/kg). Pretreatment of mice with spiperone (D2), 7-hydroxydipropylaminotetralin (7-OH-DPAT) (D3), clozapine (D4), ketanserin (5-HT2/5-HT2C), mazindol (monoamine reuptake), prazosin (α1), and haloperidol (D2/σ) had no inhibitory effect on [11C]A-69024 uptake in the striatum. The dextrorotatory enantiomer of the dopamine antagonist butaclamol inhibited striatal uptake, while the less active isomer (-)-butaclamol did not. [11C]A-69024 binding was inhibited by unlabeled A-69024 in a dose dependent manner (ED50 = 0.3 mg/kg) in the striatum while no change occurred in the cerebellum. [11C]A-69024 warrants further investigation as a PET ligand for examination of central dopamine D1 receptors in humans.
AB - [11C]A-69024, (±)-1-(2-bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-2-[1 1C]methyl-1,2,3,4-tetra-hydroisoquinoline, is a specific and selective dopamine D1 radiotracer. The in vivo biodistribution of this novel radioligand in mice showed a high uptake in the striatum (6.7%ID/g) at 5 min, followed by clearance with a half-life of 16.1 min. As a measure of specificity, the striatal/cerebellar ratio reached a maximum of 7.4 at 30 min post-injection. Radioactivity in the striatum was reduced to the level of the cerebellum by pre-adminstration of the D1 antagonist SCH 23390 (1 mg/kg). Pretreatment of mice with spiperone (D2), 7-hydroxydipropylaminotetralin (7-OH-DPAT) (D3), clozapine (D4), ketanserin (5-HT2/5-HT2C), mazindol (monoamine reuptake), prazosin (α1), and haloperidol (D2/σ) had no inhibitory effect on [11C]A-69024 uptake in the striatum. The dextrorotatory enantiomer of the dopamine antagonist butaclamol inhibited striatal uptake, while the less active isomer (-)-butaclamol did not. [11C]A-69024 binding was inhibited by unlabeled A-69024 in a dose dependent manner (ED50 = 0.3 mg/kg) in the striatum while no change occurred in the cerebellum. [11C]A-69024 warrants further investigation as a PET ligand for examination of central dopamine D1 receptors in humans.
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U2 - 10.1016/0969-8051(94)00086-Y
DO - 10.1016/0969-8051(94)00086-Y
M3 - Article
C2 - 7767316
AN - SCOPUS:0028986392
SN - 0969-8051
VL - 22
SP - 221
EP - 226
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 2
ER -