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

Nuclear Medicine and Biology
M KassiouB Mazière

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 ...Continue Reading

References

Feb 11, 1992·Trends in Pharmacological Sciences·D R Sibley, F J Monsma
Jan 1, 1991·International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes·C HalldinG Sedvall
Aug 3, 1989·European Journal of Pharmacology·D J KerkmanJ W Kebabian
Jan 1, 1993·Annual Review of Pharmacology and Toxicology·O CivelliD K Grandy

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Citations

Dec 24, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ana M CatafauMarc Laruelle
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Olaf PranteAshutosh Banerjee
Sep 10, 2020·Nuclear Medicine and Biology·Heinz H Coenen, Johannes Ermert

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