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.
PET studies using [11C]GF120918 were conducted on P-gp and/or Bcrp knockout mice as well as wild-type mice.
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.
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.
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We are grateful to Mrs. Yukio Nakamura (Tokyo Nuclear Services), Nobuki Nengaki (SHI Accelerator Service, SAS), Masanao Ogawa (SAS), Yuichiro Yoshida (SAS), and Hisashi Suzuki (National Institute of Radiological Sciences, NIRS) for their technical assistance with the radiosynthesis. We thank the staff of Cyclotron Operation Section NIRS for their technical assistance in radioisotope production and the staff of the Department of Molecular Probes NIRS for assistance. This study was partially supported by consignment expenses from the Molecular Imaging Program from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of the Japanese Government.
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Kawamura, K., Yamasaki, T., Konno, F. et al. Evaluation of Limiting Brain Penetration Related to P-glycoprotein and Breast Cancer Resistance Protein Using [11C]GF120918 by PET in Mice. Mol Imaging Biol 13, 152–160 (2011). https://doi.org/10.1007/s11307-010-0313-1
- Positron emission tomography (PET)
- P-glycoprotein (P-gp)
- Breast cancer resistance protein (BCRP)