PT - JOURNAL ARTICLE AU - Tadayuki Takashima AU - Chunyong Wu AU - Misato Takashima-Hirano AU - Yumiko Katayama AU - Yasuhiro Wada AU - Masaaki Suzuki AU - Hiroyuki Kusuhara AU - Yuichi Sugiyama AU - Yasuyoshi Watanabe TI - Evaluation of Breast Cancer Resistance Protein Function in Hepatobiliary and Renal Excretion Using PET with <sup>11</sup>C-SC-62807 AID - 10.2967/jnumed.112.110254 DP - 2013 Feb 01 TA - Journal of Nuclear Medicine PG - 267--276 VI - 54 IP - 2 4099 - http://jnm.snmjournals.org/content/54/2/267.short 4100 - http://jnm.snmjournals.org/content/54/2/267.full SO - J Nucl Med2013 Feb 01; 54 AB - A 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 11C-SC-62807 in mice. Methods: Serial abdominal PET scans were collected in wild-type and Bcrp knockout (Bcrp–/–) mice after intravenous injection of 11C-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 (CLint,bile,liver and CLint,urine,kidney, respectively). Results: SC-62807 is an in vitro substrate of mouse Bcrp and human BCRP. Radioactivity associated with 11C-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 CLint,bile,liver and the CLint,urine,kidney were significantly lower in Bcrp–/– mice (74% ± 10% and 99% ± 1% lower than controls, respectively). We also found that 11C-SC-62807 is a substrate of the organic anion-transporting polypeptides OATP1B1 and OATP1B3 in vitro. Conclusion: The present study demonstrated that Bcrp plays a significant role in the efflux of 11C-SC-62807 in mouse liver and kidney. We also demonstrated the feasibility of PET using 11C-SC-62807 to study the activity of BCRP in humans.