期刊
NUCLEAR MEDICINE AND BIOLOGY
卷 36, 期 1, 页码 3-10出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.nucmedbio.2008.10.003
关键词
Adenosine A(3) receptor; G-protein-coupled receptor; Nucleoside; Purines; Receptor binding; Bromine-76
资金
- Intramural Research Programs of NIBIB and NIDDK
- National Institutes of Health, Bethesda, MD
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [ZIFEB000001, Z02EB000001, ZIAEB000001, Z01EB000001] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [Z01DK031117, ZIADK031117] Funding Source: NIH RePORTER
Introduction: Bromine-76-radiolabeled analogues of previously reported high-affinity A(3) adenosine receptor (A(3)AR) nucleoside ligands have been prepared as potential radiotracers for positron emission tomography. Methods: The radiosyntheses were accomplished by oxidative radiobromination on the N-6-benzyl moiety of trimethyltin precursors. Biodistribution studies of the kinetics Of uptake were conducted in awake rats. Results: We prepared an agonist ligand {[Br-76](1'S,2'R,3'S,4'R,5'S)-4'-{2-chloro-6-[(3-bromophenylmethyl)amino]purin-9-yl}-1'-(methylaminocarbonyl)bicyclo[3.1.0]hexane-2',3'-diol (MRS3581)} in 59% radiochemical yield with a specific activity of 19.5 GBq/mu mol and all antagonist ligand {[Br-76](1'R,2'R,3'S,4'R,5'S)-4'-(6-(3-bromobenzylamino)-2-clhloro-9H-purin-9-yl)bicyclo[3.1.0]hexane-2',3'-diol (MRS5147) in 65% radiochemical yield with a specific activity of 22 GBq/mu mol. The resultant products exhibited the expected high affinity (K-i similar to 0.6 nM) and specific binding at the human A(3)AR in vitro. Biodistribution studies in the rat showed uptake in the organs of excretion and metabolism. The antagonist MRS5147 exhibited increasing uptake in testes, an organ that contains significant quantities of A(3)AR, over a 2-h time course, which suggests the presence of a specific A(3)AR retention mechanism. Conclusion: We were able to compare uptake of the [Br-76]-labeled antagonist MRS5147 to [Br-76]agonist MRS3581. The antagonist MRS5147 shows increasing uptake in the testes, an A(3)AR-rich tissue, suggesting that this ligand may have promise as a molecular imaging agent. Published by Elsevier Inc.
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