トラマツ チエ
  寅松 千枝
   所属   医学部 医学科(東京女子医科大学病院)
   職種   非常勤講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Noninvasive and quantitative assessment of the function of multidrug resistance-associated protein 1 in the living brain.
掲載誌名 正式名:Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
略  称:J Cereb Blood Flow Metab
ISSNコード:15597016/0271678X
掲載区分国外
巻・号・頁 29(3),pp.504-11
著者・共著者 Okamura Toshimitsu†*, Kikuchi Tatsuya, Okada Maki, Toramatsu Chie, Fukushi Kiyoshi, Takei Makoto, Irie Toshiaki
発行年月 2009/03
概要 Multidrug resistance-associated protein 1 (MRP1) acts as a defense mechanism by pumping xenobiotics and endogenous metabolites out of the brain. The currently available techniques for studying brain-to-blood efflux have significant limitations related to either their invasiveness or the qualitative assessment. Here, we describe an in vivo method, which overcomes these limitations for assessing MRP1 function, using positron emission tomography (PET) and a PET probe. 6-Bromo-7-[(11)C]methylpurine was designed to readily enter the brain after intravenous administration and to be efficiently converted to its glutathione conjugate (MRP1 substrate) in situ. Dynamic PET scan provided the brain time-activity curve after injection of 6-bromo-7-[(11)C]methylpurine into mice. The efflux rate of the substrate was kinetically estimated to be 1.4 h(-1) with high precision. Moreover, knockout of Mrp1 gene caused approximately a 90% reduction of the efflux rate, compared with wild-type mice. In conclusion, our method allows noninvasive and quantitative assessment for MRP1 function in the living brain.
DOI 10.1038/jcbfm.2008.135
PMID 18985052