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P-Glycoprotein, not BCRP, Limits the Brain Uptake of [(18)F]Mefway in Rodent Brain

Authors
 Jae Yong Choi  ;  Jin Sook Song  ;  Minkyung Lee  ;  Woon-Ki Cho  ;  Jin Chung  ;  Chul Hyoung Lyoo  ;  Chul Hoon Kim  ;  Jiae Park  ;  Kyo Chul Lee  ;  Kyeong Min Kim  ;  Jee Hae Kang  ;  Myung Ae Bae  ;  Young Hoon Ryu 
Citation
 Molecular Imaging and Biology, Vol.18(2) : 267-73, 2016 
Journal Title
 Molecular Imaging and Biology 
ISSN
 1536-1632 
Issue Date
2016
MeSH
ATP Binding Cassette Transporter, Sub-Family G, Member 2/metabolism* ; ATP-Binding Cassette, Sub-Family B, Member 1/metabolism* ; Animals ; Brain/diagnostic imaging ; Brain/metabolism* ; Fluorine Radioisotopes/pharmacokinetics* ; Male ; Mice, Knockout ; Piperazines/blood ; Piperazines/pharmacokinetics* ; Positron-Emission Tomography ; Pyridines/blood ; Pyridines/pharmacokinetics* ; Quinolines/administration & dosage ; Rats, Sprague-Dawley
Keywords
Breast cancer resistance protein ; P-glycoprotein ; PET ; [18F]Mefway
Abstract
PURPOSE: 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. PROCEDURES: [(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.
Full Text
http://link.springer.com/article/10.1007/s11307-015-0883-z
DOI
10.1007/s11307-015-0883-z
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실)
Yonsei Authors
김철훈(Kim, Chul Hoon) ORCID logo https://orcid.org/0000-0002-7360-429X
류철형(Lyoo, Chul Hyoung)
유영훈(Ryu, Young Hoon)
최재용(Choi, Jae Yong)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146590
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