P-Glycoprotein,not BCRP,Limits the Brain Uptake of [18F]Mefway in Rodent Brain |
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| 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 |
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| Affiliation: | 1.Department of Nuclear Medicine,Gangnam Severance Hospital, Yonsei University College of Medicine,Gangnam-Gu,Korea;2.Drug Discovery Platform Technology Group, Drug Discovery Division,Korea Research Institute of Chemical Technology,Daejeon,Republic of Korea;3.Department of Nuclear Medicine,Inha University College of Medicine, Inha University Hospital,Incheon,Korea;4.Department of Radiology,Ewha Womans University School of Medicine,Seoul,Korea;5.Department of Radiology,Yonsei University College of Medicine,Seoul,Korea;6.Department of Neurology,Gangnam Severance Hospital, Yonsei University College of Medicine,Seoul,Korea;7.Department of Pharmacology,Yonsei University College of Medicine,Seoul,Korea;8.Brain Korea 21 PLUS Project for Medical Science,Yonsei University College of Medicine,Seoul,Korea;9.Molecular Imaging Research Center,Korea Institute of Radiological and Medical Sciences,Seoul,Korea;10.Department of Chemistry and Biochemistry,Swarthmore College,Swarthmore,USA |
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| Abstract: | PurposeThe aim of this study was to determine whether the brain uptake of [18F]Mefway is influenced by the action of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) in rodents.Procedures[18F]Mefway was applied to rats pharmacologically inhibited with tariquidar (TQD) and to genetically disrupted mice.ResultsPretreatment 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[18F]Mefway is modulated by P-gp, and not by Bcrp in rodents. |
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