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

Authors

    • Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological Sciences
  • Tomoteru Yamasaki
    • Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological Sciences
  • Fujiko Konno
    • Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological Sciences
  • Joji Yui
    • Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological Sciences
  • Akiko Hatori
    • Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological Sciences
  • Kazuhiko Yanamoto
    • Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological Sciences
  • Hidekatsu Wakizaka
    • Department of Biophysics, Molecular Imaging CenterNational Institute of Radiological Sciences
  • Makoto Takei
    • Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological Sciences
    • Tokyo Nuclear Services Co., Ltd.
  • Yuichi Kimura
    • Department of Biophysics, Molecular Imaging CenterNational Institute of Radiological Sciences
  • Toshimitsu Fukumura
    • Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological Sciences
  • Ming-Rong Zhang
    • Department of Molecular Probes, Molecular Imaging CenterNational Institute of Radiological Sciences
Research Article

DOI: 10.1007/s11307-010-0313-1

Cite this article as:
Kawamura, K., Yamasaki, T., Konno, F. et al. Mol Imaging Biol (2011) 13: 152. doi:10.1007/s11307-010-0313-1

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-11GF120918Elacridar

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010