2-11C]isopropyl-, [1-11C]ethyl-, and [11C]methyl-labeled phenoxyphenyl acetamide derivatives as positron emission tomography ligands for the peripheral benzodiazepine receptor: radiosynthesis, uptake, and in vivo binding in brain

Journal of Medicinal Chemistry
Ming-Rong ZhangKazutoshi Suzuki

Abstract

The peripheral benzodiazepine receptor (PBR) is widely expressed in peripheral tissues, blood cells, and in glia cells in the brain. We have previously developed two positron emission tomography (PET) ligands, N-(2-[(11)C],5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([(11)C]2) and its [(18)F]fluoroethyl analogue ([(18)F]6), for the current investigation of PBR in the human brain. The aim of this study was to label the potent PBR agonist N-(4-chloro-2-phenoxyphenyl)-N-(isopropoxybenzyl)acetamide (3) and its ethyl (7) and methyl (8) homologues with (11)C and to evaluate them as PET ligands for PBR with mice, rats, and monkeys. Ligands [(11)C]3, [(11)C]7, and [(11)C]8 were synthesized by alkylation of phenol precursor 9 with 2-[2-(11)C]iodopropane ([(11)C]10), [1-(11)C]iodoethane ([(11)C]11), and [(11)C]iodomethane ([(11)C]12), respectively. The alkylating agent [(11)C]10 or [(11)C]11 was prepared by reacting CH(3)MgBr with [(11)C]CO(2), followed by reduction with LiAlH(4) and iodination with HI. In vitro quantitative autoradiography determined that 3, 7, and 8 had potent binding affinities (K(i) = 0.07-0.19 nM) for PBR in the rat brain. These [(11)C]ligands could pass across the blood-brain barrier and enter the rat ...Continue Reading

References

Sep 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·C Braestrup, R F Squires
Mar 16, 1984·European Journal of Pharmacology·J BenavidesG Le Fur
Sep 1, 1997·General Pharmacology·D M Zisterer, D C Williams
Jul 27, 1999·The Journal of Steroid Biochemistry and Molecular Biology·M CultyV Papadopoulos
Aug 17, 2002·The Journal of Pharmacology and Experimental Therapeutics·Jean Pierre FaureVassilios Papadopoulos
Apr 27, 2005·Brain Research. Brain Research Reviews·Michael KassiouRichard B Banati

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Citations

Dec 7, 2007·European Journal of Nuclear Medicine and Molecular Imaging·Filomena MattnerAndrew Katsifis
Oct 2, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Fabien ChauveauBertrand Tavitian
Apr 13, 2011·European Journal of Nuclear Medicine and Molecular Imaging·Filomena MattnerAndrew Katsifis
Apr 2, 2014·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Thomas BourdierAndrew Katsifis
Jul 30, 2017·Journal of Labelled Compounds & Radiopharmaceuticals·Lonneke RotteveelAlbert D Windhorst
Oct 28, 2014·Brain Pathology·Guo-Jun LiuRichard B Banati
Dec 16, 2017·Nuclear Medicine and Molecular Imaging·Md Maqusood AlamSang-Yoon Lee

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