Jae Yong Choi1, Jin Sook Song2, Minkyung Lee3, Woon-Ki Cho2, Jin Chung4,5, Chul Hyoung Lyoo6, Chul Hoon Kim7,8, Jiae Park9, Kyo Chul Lee9, Kyeong Min Kim9, Jee Hae Kang10, Myung Ae Bae11, Young Hoon Ryu12. 1. Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-Gu, Seoul, 135-720, 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, 500 College Avenue, Swarthmore, PA, USA. 11. Drug Discovery Platform Technology Group, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea. mbae@krict.re.kr. 12. Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712, Eonjuro, Gangnam-Gu, Seoul, 135-720, Korea. ryuyh@yuhs.ac.
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.
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.
Entities:
Keywords:
Breast cancer resistance protein; P-glycoprotein; PET; [18F]Mefway
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