Tadayuki Takashima, Chunyong Wu, Misato Takashima-Hirano, Yumiko Katayama, Yasuhiro Wada, Masaaki Suzuki, Hiroyuki Kusuhara, Yuichi Sugiyama, Yasuyoshi Watanabe
Molecular Probe Dynamics Laboratory, RIKEN Center for Molecular Imaging Science, Kobe, Japan. ttakashima@riken.jp
Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2013 FebA quantitative PET imaging method was used to assess the in vivo kinetics of hepatobiliary and renal excretion of the breast cancer resistance protein (Bcrp) substrate (11)C-SC-62807 in mice. Serial abdominal PET scans were collected in wild-type and Bcrp knockout (Bcrp(-/-)) mice after intravenous injection of (11)C-SC-62807. Venous blood samples and PET images were obtained at frequent intervals up to 30 min after radiotracer administration. Dynamic PET data were analyzed to determine the canalicular and brush-border efflux clearances in the liver and kidney (CL(int,bile,liver) and CL(int,urine,kidney), respectively). SC-62807 is an in vitro substrate of mouse Bcrp and human BCRP. Radioactivity associated with (11)C-SC-62807 was predominantly found in the blood, liver, bile, and urine 30 min after administration. Both biliary and urinary excretion of radioactivity was markedly lower in Bcrp(-/-) mice than in wild-type mice, suggesting greater systemic exposure in Bcrp(-/-) mice. Both the CL(int,bile,liver) and the CL(int,urine,kidney) were significantly lower in Bcrp(-/-) mice (74% ± 10% and 99% ± 1% lower than controls, respectively). We also found that (11)C-SC-62807 is a substrate of the organic anion-transporting polypeptides OATP1B1 and OATP1B3 in vitro. The present study demonstrated that Bcrp plays a significant role in the efflux of (11)C-SC-62807 in mouse liver and kidney. We also demonstrated the feasibility of PET using (11)C-SC-62807 to study the activity of BCRP in humans.
Tadayuki Takashima, Chunyong Wu, Misato Takashima-Hirano, Yumiko Katayama, Yasuhiro Wada, Masaaki Suzuki, Hiroyuki Kusuhara, Yuichi Sugiyama, Yasuyoshi Watanabe. Evaluation of breast cancer resistance protein function in hepatobiliary and renal excretion using PET with 11C-SC-62807. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2013 Feb;54(2):267-76
PMID: 23287578
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