Evaluation of Breast Cancer Resistance Protein Function in Hepatobiliary and Renal Excretion Using PET with 11C-SC-62807
| Autor: | Chunyong Wu, Hiroyuki Kusuhara, Yumiko Katayama, Masaaki Suzuki, Yuichi Sugiyama, Yasuyoshi Watanabe, Misato Takashima-Hirano, Yasuhiro Wada, Tadayuki Takashima |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Abcg2 Urine Kidney Gastroenterology Mice Internal medicine medicine ATP Binding Cassette Transporter Subfamily G Member 2 Animals Humans Radiology Nuclear Medicine and imaging Carbon Radioisotopes Biliary Tract Chromatography High Pressure Liquid Sulfonamides Dose-Response Relationship Drug biology business.industry Kidney metabolism Venous blood Neoplasm Proteins Kinetics Dose–response relationship HEK293 Cells Endocrinology medicine.anatomical_structure Gene Expression Regulation Liver Models Chemical Area Under Curve Positron-Emission Tomography Renal physiology biology.protein Pyrazoles ATP-Binding Cassette Transporters Efflux business |
| Zdroj: | Journal of Nuclear Medicine. 54:267-276 |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.112.110254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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