Document Detail


Evaluation of Breast Cancer Resistance Protein Function in Hepatobiliary and Renal Excretion Using PET with 11C-SC-62807.
MedLine Citation:
PMID:  23287578     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 (11)C-SC-62807 in mice. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
Authors:
Tadayuki Takashima; Chunyong Wu; Misato Takashima-Hirano; Yumiko Katayama; Yasuhiro Wada; Masaaki Suzuki; Hiroyuki Kusuhara; Yuichi Sugiyama; Yasuyoshi Watanabe
Related Documents :
17210668 - Protection against cryptococcosis by using a murine gamma interferon-producing cryptoco...
16362898 - T cells require tumor necrosis factor-alpha to provide protective immunity in mice infe...
18074098 - An insufficient anti-inflammatory cytokine response in mouse brain is associated with i...
15208038 - Systemic and placental productions of tumor necrosis factor contribute to induce fetal ...
7828718 - Stimulation of transforming growth factor-beta 1 transcription by cyclosporine.
7636258 - Transforming growth factor-beta stimulates arginase activity in macrophages. implicatio...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-3
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  -     ISSN:  1535-5667     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
RIKEN Center for Molecular Imaging Science, Kobe, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Respiratory Motion Correction in Oncologic PET Using T1-Weighted MR Imaging on a Simultaneous Whole-...
Next Document:  Membrane tubulovesicular extensions (cytonemes): secretory and adhesive cellular organelles.