Premium
Effects of P‐gp and Bcrp as brain efflux transporters on the uptake of [ 18 F]FPEB in the murine brain
Author(s) -
Jung KiHye,
Oh Se Jong,
Kang Kyung Jun,
Han Sang Jin,
Nam Kyung Rok,
Park Ji Ae,
Lee Kyo Chul,
Lee Yong Jin,
Choi Jae Yong
Publication year - 2019
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.22123
Subject(s) - abcg2 , p glycoprotein , efflux , transporter , knockout mouse , pharmacology , chemistry , atp binding cassette transporter , biology , multiple drug resistance , receptor , biochemistry , gene , antibiotics
The purpose of this study was to determine whether the brain uptake of [ 18 F]FPEB is influenced by P‐glycoprotein (P‐gp) and breast cancer resistance protein (Bcrp) as efflux transporters in rodents. To assess this possible modulation, positron emission tomography studies were performed in animal models of pharmacological or genetic ablation of these transporters. Compared with the control conditions, when P‐gp was blocked with tariquidar, there was an 8%–12% increase in the brain uptake of [ 18 F]FPEB. In P‐gp knockout mice, such as Mdr1a/b (−/−) and Mdr1a/b (−/−) Bcrp1 (−/−) , genetic ablation models, there was an increment of 8%–53% in [ 18 F]FPEB uptake compared with that in the wild‐type mice. In contrast, Bcrp knockout mice showed a decrement of 5%–12% uptake and P‐gp/Bcrp knockout group displayed an increment of 5%–17% compared with wild type. These results indicate that [ 18 F]FPEB is possibly a weak substrate for P‐gp.