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- Title
P-Glycoprotein, not BCRP, Limits the Brain Uptake of [(18)F]Mefway in Rodent Brain.
- Authors
Choi, Jae; Song, Jin; Lee, Minkyung; Cho, Woon-Ki; Chung, Jin; Lyoo, Chul; Kim, Chul; Park, Jiae; Lee, Kyo; Kim, Kyeong; Kang, Jee; Bae, Myung; Ryu, Young; Choi, Jae Yong; Song, Jin Sook; Lyoo, Chul Hyoung; Kim, Chul Hoon; Lee, Kyo Chul; Kim, Kyeong Min; Kang, Jee Hae
- Abstract
<bold>Purpose: </bold>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.<bold>Procedures: </bold>[(18)F]Mefway was applied to rats pharmacologically inhibited with tariquidar (TQD) and to genetically disrupted mice.<bold>Results: </bold>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.<bold>Conclusions: </bold>[(18)F]Mefway is modulated by P-gp, and not by Bcrp in rodents.
- Subjects
P-glycoprotein; BREAST cancer; ANIMAL models in research; KNOCKOUT mice; PROTEIN conformation
- Publication
Molecular Imaging & Biology, 2016, Vol 18, Issue 2, p267
- ISSN
1536-1632
- Publication type
journal article
- DOI
10.1007/s11307-015-0883-z