Document Detail


Dynamic MRI using iron oxide nanoparticles to assess early vascular effects of antiangiogenic versus corticosteroid treatment in a glioma model.
MedLine Citation:
PMID:  19142191     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The vascular effects of antiangiogenic treatment may pose problems for evaluating brain tumor response based on contrast-enhanced magnetic resonance imaging (MRI). We used serial dynamic contrast-enhanced MRI at 12 T to assess vascular responses to antiangiogenic versus steroid therapy. Athymic rats with intracerebral U87MG human glioma (n=17) underwent susceptibility-weighted perfusion MRI with ferumoxytol, a solely intravascular ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle, followed by T1-weighted dynamic gadodiamide-enhanced MRI to measure vascular permeability. Rats were imaged before and after 24, 48, and 72 h of treatment with the antiangiogenic agent bevacizumab or the corticosteroid dexamethasone. Contrast agent extravasation was seen rapidly after gadodiamide, but not with ferumoxytol administration. Bevacizumab significantly decreased the blood volume and decreased permeability in tumors as determined by increased time-to-peak enhancement. A single dose of 45 mg/kg bevacizumab resulted in changes analogous to dexamethasone given in an extremely high dose (12 mg/kg per day), and was significantly more effective than dexamethasone at 2 mg/kg per day. We conclude that dynamic perfusion MRI measurements with ferumoxytol USPIO to assess cerebral blood volume, along with dynamic gadodiamide-enhanced MR to assess vascular permeability, hold promise in more accurately detecting therapeutic responses to antiangiogenic therapy.
Authors:
Csanad G Varallyay; Leslie L Muldoon; Seymur Gahramanov; Yingjen J Wu; James A Goodman; Xin Li; Martin M Pike; Edward A Neuwelt
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-01-14
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  29     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-01     Completed Date:  2009-05-06     Revised Date:  2010-10-04    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  853-60     Citation Subset:  IM    
Affiliation:
Department of Neuroradiology, Universitätsklinikum Würzburg, Würzburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adrenal Cortex Hormones / therapeutic use*
Angiogenesis Inhibitors / therapeutic use*
Animals
Antibodies, Monoclonal / therapeutic use
Capillary Permeability
Cerebrovascular Circulation / drug effects
Dexamethasone / therapeutic use
Disease Models, Animal
Drug Monitoring / methods
Ferric Compounds / diagnostic use*
Gadolinium DTPA / diagnostic use
Glioma / diagnosis,  drug therapy*
Humans
Kinetics
Magnetic Resonance Imaging / methods*
Nanoparticles / diagnostic use*
Rats
Grant Support
ID/Acronym/Agency:
NS33618/NS/NINDS NIH HHS; NS44687/NS/NINDS NIH HHS; NS53468/NS/NINDS NIH HHS; R01 CA137488-14A1/CA/NCI NIH HHS; R01 NS053468-03/NS/NINDS NIH HHS; R37 NS044687-26/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Adrenal Cortex Hormones; 0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal; 0/Ferric Compounds; 0/bevacizumab; 122795-43-1/gadodiamide; 1309-37-1/ferric oxide; 50-02-2/Dexamethasone; 80529-93-7/Gadolinium DTPA
Comments/Corrections

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