(+)-[76Br]A-69024: A non-benzazepine radioligand for studies of dopamine D1 receptors using PET

Kassiou, Michael, Loc’h, Christian, Bottlaender, Michel, Mardon, Karine, Ottaviani, Michele, Coulon, Christine, Katsifis, Andrew and Maziere, Bernard (2002) (+)-[76Br]A-69024: A non-benzazepine radioligand for studies of dopamine D1 receptors using PET. Nuclear Medicine and Biology, 29 3: 295-302. doi:10.1016/S0969-8051(01)00306-7

Author Kassiou, Michael
Loc’h, Christian
Bottlaender, Michel
Mardon, Karine
Ottaviani, Michele
Coulon, Christine
Katsifis, Andrew
Maziere, Bernard
Title (+)-[76Br]A-69024: A non-benzazepine radioligand for studies of dopamine D1 receptors using PET
Formatted title
(+)-[76Br]A-69024: A non-benzazepine radioligand for studies of dopamine D1 receptors using PET
Journal name Nuclear Medicine and Biology   Check publisher's open access policy
ISSN 0969-8051
Publication date 2002
Sub-type Article (original research)
DOI 10.1016/S0969-8051(01)00306-7
Volume 29
Issue 3
Start page 295
End page 302
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Abstract (+)-[76Br]A-69024 is a specific and enantioselective dopamine D1 receptor radioligand. The Bmax of (+)-[76Br]A-69024 measured in vitro on rat striatum membranes was 320 ± 25 fmoles/mg protein with an apparent dissociation constant of Kd = 0.6 ± 0.1 nM. The inactive enantiomer, (-)-[76Br]A-69024, displayed no affinity in the same assay. In vivo, the biodistribution (+)-[76Br]A-69024 in rats showed a rapid and high uptake in the striatum (1% ID/g), followed by a slow wash out. The striatum/cerebellum concentration ratio (index of specific binding) reached a maximum value of 10 at 60 minutes post injection. A tissue to cerebellum ratio of 2.8 and 1.5 was also observed for frontal and posterior cortex respectively. With the pharmacologically inactive enantiomer, (-)-[76Br]A-69024, the brain uptake was determined to be non specific since a striatum/cerebellum ratio of approximately 1 was observed throughout the time course of the experiment. The selectivity of (+)-[76Br]A-69024 uptake was demonstrated in competition experiments. The specific uptake in the striatum and cortical regions was completely prevented after administration of the D1 antagonist SCH 23390. Pre-treatment of rats with unlabelled (+)A-69024 also displayed the same regional inhibition of (+)-[76Br]A-69024 uptake. Pre-administration of rats with spiperone (D2) and ketanserin (5-HT2/5-HT2C) showed no inhibitory effect on (+)-[76Br]A-69024 uptake in any brain region. Using (+)-[76Br]A-69024, PET study in baboon demonstrated a preferential accumulation of the radioactivity in the striatum, frontal and posterior cortex which was displaced to the level of the cerebellum by SCH 23390. These results suggest that (+)-[76Br]A-69024 may deserve further investigation as a potential radioligand for studying striatal and cortical dopamine D1 receptors using PET. © 2002 Elsevier Science Inc. All rights reserved.
Keyword Bromine-76
Dopamine D1 receptors
Positron emission tomography
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Advanced Imaging Publications
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Created: Fri, 26 Nov 2010, 16:14:45 EST by Dr Karine Mardon on behalf of Centre for Advanced Imaging