Research Article

Molecular Imaging and Biology

, Volume 13, Issue 1, pp 152-160

First online:

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

  • Kazunori KawamuraAffiliated withDepartment of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences Email author 
  • , Tomoteru YamasakiAffiliated withDepartment of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences
  • , Fujiko KonnoAffiliated withDepartment of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences
  • , Joji YuiAffiliated withDepartment of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences
  • , Akiko HatoriAffiliated withDepartment of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences
  • , Kazuhiko YanamotoAffiliated withDepartment of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences
  • , Hidekatsu WakizakaAffiliated withDepartment of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences
  • , Makoto TakeiAffiliated withDepartment of Molecular Probes, Molecular Imaging Center, National Institute of Radiological SciencesTokyo Nuclear Services Co., Ltd.
  • , Yuichi KimuraAffiliated withDepartment of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences
    • , Toshimitsu FukumuraAffiliated withDepartment of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences
    • , Ming-Rong ZhangAffiliated withDepartment of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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 K 1 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