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

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 New York",

number = "2",

}

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 - http://www.scopus.com/inward/record.url?scp=84959912302&partnerID=8YFLogxK

U2 - 10.1007/s11307-015-0883-z

DO - 10.1007/s11307-015-0883-z

M3 - Article

C2 - 26250653

AN - SCOPUS:84959912302

SN - 1536-1632

VL - 18

SP - 267

EP - 273

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 2