Document Detail


Non-invasive imaging of barriers to drug delivery in tumors.
MedLine Citation:
PMID:  18638494     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Solid tumors often develop high interstitial fluid pressure (IFP) as a result of increased water leakage and impaired lymphatic drainage, as well as changes in the extracellular matrix composition and elasticity. This high fluid pressure forms a barrier to drug delivery and hence, resistance to therapy. We have developed techniques based on contrast enhanced magnetic resonance imaging for mapping in tumors the vascular and transport parameters determining the delivery efficiency of blood borne substances. Sequential images are recorded during continuous infusion of a Gd-based contrast agent and analyzed according to a new physiological model, yielding maps of microvascular transfer constants, as well as outward convective interstitial transfer constants and steady state interstitial contrast agent concentrations both reflecting IFP distribution. We further demonstrated in non small cell human lung cancer xenografts the capability of our techniques to monitor in vivo collagenase induced increase in contrast agent delivery as a result of decreased IFP. These techniques can be applied to test drugs that affect angiogenesis and modulate interstitial fluid pressure and has the potential to be extended to cancer patients for assessing resistance to drug delivery.
Authors:
Yaron Hassid; Erez Eyal; Raanan Margalit; Edna Furman-Haran; Hadassa Degani
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-06-27
Journal Detail:
Title:  Microvascular research     Volume:  76     ISSN:  1095-9319     ISO Abbreviation:  Microvasc. Res.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-26     Completed Date:  2008-11-03     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0165035     Medline TA:  Microvasc Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  94-103     Citation Subset:  IM    
Affiliation:
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Animals
Biological Transport / drug effects,  physiology
Capillaries / metabolism,  pathology,  physiopathology
Carcinoma, Non-Small-Cell Lung / metabolism,  pathology,  physiopathology
Cell Line, Tumor
Collagenases / administration & dosage,  pharmacology
Extracellular Fluid / drug effects,  physiology
Extravasation of Diagnostic and Therapeutic Materials / metabolism,  pathology,  physiopathology*
Female
Gadolinium DTPA / administration & dosage,  metabolism,  pharmacokinetics
Humans
Image Processing, Computer-Assisted
Injections, Intravenous
Lung Neoplasms / metabolism,  pathology,  physiopathology
Magnetic Resonance Imaging / methods*
Mice
Mice, Nude
Microscopy, Fluorescence
Neoplasms, Experimental / metabolism,  pathology,  physiopathology*
Pharmaceutical Preparations / administration & dosage,  metabolism*
Pressure
Transplantation, Heterologous
Grant Support
ID/Acronym/Agency:
CA 422238/CA/NCI NIH HHS; R01 CA042238-14/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Pharmaceutical Preparations; 80529-93-7/Gadolinium DTPA; EC 3.4.24.-/Collagenases
Comments/Corrections

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