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
May 1, 1992·Journal of Neurochemistry·M GavishR Weizman
Jul 1, 1989·Annals of Nuclear Medicine·K HashimotoM Kojima
Dec 1, 1983·Journal of Neurochemistry·J BenavidesG Le Fur
Mar 16, 1984·European Journal of Pharmacology·J BenavidesG Le Fur
Mar 27, 1995·Brain Research·J T NearyM D Norenberg
Aug 29, 1997·Journal of Medicinal Chemistry·A CappelliC Manzoni
Sep 1, 1997·General Pharmacology·D M Zisterer, D C Williams
May 13, 1999·Life Sciences·S OkuyamaK Tomisawa
Jul 27, 1999·The Journal of Steroid Biochemistry and Molecular Biology·M CultyV Papadopoulos
Feb 15, 2001·Journal of Medicinal Chemistry·M MatarreseF Fazio
Aug 17, 2002·The Journal of Pharmacology and Experimental Therapeutics·Jean Pierre FaureVassilios Papadopoulos
Jun 26, 2003·European Neurology·Jan J VersijptJakob Korf
Apr 23, 2004·Synapse·Jun MaedaKazutoshi Suzuki
Apr 27, 2005·Brain Research. Brain Research Reviews·Michael KassiouRichard B Banati
May 6, 2005·European Journal of Nuclear Medicine and Molecular Imaging·F MattnerD O Willenborg
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
Dec 1, 2015·ACS Chemical Neuroscience·Xintong ZhangWenbin Zeng
Jul 23, 2015·Disease Markers·F MattnerA 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
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Annelaure DamontFrédéric Dollé
Aug 8, 2020·EJNMMI Research·Matthew ZammitBradley T Christian
Aug 19, 2009·ChemMedChem·Tiziano TuccinardiAdriano Martinelli
Oct 28, 2014·Brain Pathology·Guo-Jun LiuRichard B Banati
Dec 16, 2017·Nuclear Medicine and Molecular Imaging·Md Maqusood AlamSang-Yoon Lee
Dec 11, 2007·Journal of Medicinal Chemistry·Emmanuelle BriardVictor W Pike
Aug 7, 2021·RSC Medicinal Chemistry·Filomena MattnerMichael Fulham