Molecular Imaging and Biology

, Volume 13, Issue 1, pp 152–160

Evaluation of Limiting Brain Penetration Related to P-glycoprotein and Breast Cancer Resistance Protein Using [11C]GF120918 by PET in Mice

  • Kazunori Kawamura
  • Tomoteru Yamasaki
  • Fujiko Konno
  • Joji Yui
  • Akiko Hatori
  • Kazuhiko Yanamoto
  • Hidekatsu Wakizaka
  • Makoto Takei
  • Yuichi Kimura
  • Toshimitsu Fukumura
  • Ming-Rong Zhang
Research Article

Abstract

Purpose

GF120918 has a high inhibitory effect on P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). We developed [11C]GF120918 as a positron emission tomography (PET) probe to assess if dual modulation of P-gp and BCRP is useful to evaluate brain penetration.

Procedures

PET studies using [11C]GF120918 were conducted on P-gp and/or Bcrp knockout mice as well as wild-type mice.

Results

In PET studies, the AUCbrain[0–60 min] and K1 value in P-gp/Bcrp knockout mice were nine- and 26-fold higher than that in wild-type mice, respectively. These results suggest that brain penetration of [11C]GF120918 is related to modulation of P-gp and BCRP and is limited by two transporters working together.

Conclusions

PET using [11C]GF120918 may be useful for evaluating the function of P-gp and BCRP. PET using P-gp/Bcrp knockout mice may be an effective method to understand the overall contributions the functions of P-gp and BCRP.

Key words

Positron emission tomography (PET) P-glycoprotein (P-gp) Breast cancer resistance protein (BCRP) Carbon-11 GF120918 Elacridar 

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Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010

Authors and Affiliations

  • Kazunori Kawamura
    • 1
  • Tomoteru Yamasaki
    • 1
  • Fujiko Konno
    • 1
  • Joji Yui
    • 1
  • Akiko Hatori
    • 1
  • Kazuhiko Yanamoto
    • 1
  • Hidekatsu Wakizaka
    • 2
  • Makoto Takei
    • 1
    • 3
  • Yuichi Kimura
    • 2
  • Toshimitsu Fukumura
    • 1
  • Ming-Rong Zhang
    • 1
  1. 1.Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological SciencesChibaJapan
  2. 2.Department of Biophysics, Molecular Imaging CenterNational Institute of Radiological SciencesChibaJapan
  3. 3.Tokyo Nuclear Services Co., Ltd.TokyoJapan

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