| Longitudinal investigation of permeability and distribution of macromolecules in mouse malignant transformation using PET. | |
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MedLine Citation:
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PMID: 21106723 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease. EXPERIMENTAL DESIGN: Albumin and liposomes were labeled with (64)Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability. RESULTS: From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased ∼2.5-fold to 6.6 × 10(-8) and 1.3 × 10(-8) cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of ∼6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 ± 8.1 and 7.1 ± 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin. CONCLUSIONS: PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability. |
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Authors:
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Cecilie B Rygh; Shengping Qin; Jai W Seo; Lisa M Mahakian; Hua Zhang; Roger Adamson; Jane Q Chen; Alexander D Borowsky; Robert D Cardiff; Rolf K Reed; Fitz-Roy E Curry; Katherine W Ferrara |
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Publication Detail:
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Type: Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-24 |
Journal Detail:
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Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: 17 ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-03 Completed Date: 2011-06-17 Revised Date: 2012-03-14 |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 550-9 Citation Subset: IM |
Copyright Information:
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©2010 AACR. |
Affiliation:
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Department of Physiology and Membrane Biology, University of California Davis, California, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Capillary Permeability* Carcinoma in Situ / blood supply* Cell Transformation, Neoplastic / metabolism* Copper Radioisotopes / diagnostic use Disease Progression Liposomes / metabolism* Mammary Neoplasms, Experimental / blood supply* Mice Nanoparticles / analysis Positron-Emission Tomography / methods* Serum Albumin / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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K26 RR024037-05/RR/NCRR NIH HHS; R01 CA103828-06A1/CA/NCI NIH HHS; R01 CA103828-07/CA/NCI NIH HHS; R01 CA103828-08/CA/NCI NIH HHS; R01 CA103828-09/CA/NCI NIH HHS; R01 CA134659-01A1/CA/NCI NIH HHS; R01 CA134659-02/CA/NCI NIH HHS; R01 CA134659-03/CA/NCI NIH HHS; R01 CA134659-04/CA/NCI NIH HHS; R01CA103828/CA/NCI NIH HHS; R01CA134659/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Copper Radioisotopes; 0/Liposomes; 0/Serum Albumin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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