title: P-Glycoprotein, not BCRP, Limits the Brain Uptake of [(18)F]Mefway in Rodent Brain.
abstract: OBJECTIVE
  The aim of this study was to determine whether the brain uptake of [(18)F]Mefway is influenced by the action of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) in rodents.
  
  
  METHODS
  [(18)F]Mefway was applied to rats pharmacologically inhibited with tariquidar (TQD) and to genetically disrupted mice.
  
  
  RESULTS
  Pretreatment of TQD results in 160% higher hippocampal uptake compared with control rats. In genetically disrupted mice, a maximal brain uptake value of 3.2 SUV in the triple knockout mice (tKO, Mdr1a/b((-/-))Bcrp1((-/-))) was comparable to that of the double knockout mice (dKO, Mdr1a/b((-/-))) and 2-fold those of the wild-type and Bcrp1((-/-)) knockout mice. The differences of binding values were statistically insignificant between control and experimental groups. The brain-to-plasma ratios for tKO mice were also two to five times higher than those for other groups.
  
  
  CONCLUSIONS
  [(18)F]Mefway is modulated by P-gp, and not by Bcrp in rodents.
authors.affiliation: Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-Gu, Seoul, 135-720, Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Drug Discovery Platform Technology Group, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Song
authors.affiliation: Department of Nuclear Medicine, Inha University College of Medicine, Inha University Hospital, Incheon, Korea.
authors.forename: Minkyung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Drug Discovery Platform Technology Group, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Woon-Ki
authors.initials: WK
authors.lastname: Cho
authors.affiliation: Department of Radiology, Ewha Womans University School of Medicine, Seoul, Korea.|Department of Radiology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chul Hyoung
authors.initials: CH
authors.lastname: Lyoo
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Jiae
authors.initials: J
authors.lastname: Park
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Kyeong Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Biochemistry, Swarthmore College, 500 College Avenue, Swarthmore, PA, USA.
authors.forename: Jee Hae
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Drug Discovery Platform Technology Group, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea. mbae@krict.re.kr.
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.affiliation: Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-Gu, Seoul, 135-720, Korea. ryuyh@yuhs.ac.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Ryu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D018345:Mice, Knockout; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics*; D011804:Quinolines / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; C501412:Abcg2 protein, mouse; D005462:Fluorine Radioisotopes; D010879:Piperazines; D011725:Pyridines; D011804:Quinolines; C515664:mefway; C402343:tariquidar
keywords: Breast cancer resistance protein; P-glycoprotein; PET; [18F]Mefway