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

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

doi:10.1007/s11307-015-0883-z

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

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

Department of Radiology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Purpose: The 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. 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: [¹⁸F]Mefway is modulated by P-gp, and not by Bcrp in rodents.

Original language	English
Pages (from-to)	267-273
Number of pages	7
Journal	Molecular Imaging and Biology
Volume	18
Issue number	2
DOIs	https://doi.org/10.1007/s11307-015-0883-z
State	Published - 1 Apr 2016

Bibliographical note

Funding Information:
This research was supported by the Nuclear R&D Program of the National Research Foundation of Korea (Grant No. NRF-2015M2A2A7027110).

Publisher Copyright:
© 2015, World Molecular Imaging Society.

Keywords

Breast cancer resistance protein
P-glycoprotein
PET
[F]Mefway

Access to Document

10.1007/s11307-015-0883-z

Cite this

@article{3da65041ed894d59afdc7cc231c7467c,

title = "P-Glycoprotein, not BCRP, Limits the Brain Uptake of [18F]Mefway in Rodent Brain",

abstract = "Purpose: The 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. 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: [18F]Mefway is modulated by P-gp, and not by Bcrp in rodents.",

keywords = "Breast cancer resistance protein, P-glycoprotein, PET, [F]Mefway",

author = "Choi, \{Jae Yong\} and Song, \{Jin Sook\} and Minkyung Lee and Cho, \{Woon Ki\} and Jin Chung and Lyoo, \{Chul Hyoung\} and Kim, \{Chul Hoon\} and Jiae Park and Lee, \{Kyo Chul\} and Kim, \{Kyeong Min\} and Kang, \{Jee Hae\} and Bae, \{Myung Ae\} and Ryu, \{Young Hoon\}",

note = "Funding Information: This research was supported by the Nuclear R\&D Program of the National Research Foundation of Korea (Grant No. NRF-2015M2A2A7027110). Publisher Copyright: {\textcopyright} 2015, World Molecular Imaging Society.",

year = "2016",

month = apr,

day = "1",

doi = "10.1007/s11307-015-0883-z",

language = "English",

volume = "18",

pages = "267--273",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "2",

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TY - JOUR

T1 - P-Glycoprotein, not BCRP, Limits the Brain Uptake of [18F]Mefway in Rodent Brain

AU - Choi, Jae Yong

AU - Song, Jin Sook

AU - Lee, Minkyung

AU - Cho, Woon Ki

AU - Chung, Jin

AU - Lyoo, Chul Hyoung

AU - Kim, Chul Hoon

AU - Park, Jiae

AU - Lee, Kyo Chul

AU - Kim, Kyeong Min

AU - Kang, Jee Hae

AU - Bae, Myung Ae

AU - Ryu, Young Hoon

N1 - Funding Information: This research was supported by the Nuclear R&D Program of the National Research Foundation of Korea (Grant No. NRF-2015M2A2A7027110). Publisher Copyright: © 2015, World Molecular Imaging Society.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Purpose: The 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. 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: [18F]Mefway is modulated by P-gp, and not by Bcrp in rodents.

AB - Purpose: The 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. 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: [18F]Mefway is modulated by P-gp, and not by Bcrp in rodents.

KW - Breast cancer resistance protein

KW - P-glycoprotein

KW - PET

KW - [F]Mefway

UR - https://www.scopus.com/pages/publications/84959912302

U2 - 10.1007/s11307-015-0883-z

DO - 10.1007/s11307-015-0883-z

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AN - SCOPUS:84959912302

SN - 1536-1632

VL - 18

SP - 267

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JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

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