Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 29, Issue 4, Pages 853-860Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2008.162
Keywords
bevacizumab; DCE; dexamethasone; DSC; dynamic MRI; ferumoxytol
Categories
Funding
- Veterans Administration Merit Review
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke [NS33618, NS53468, NS44687]
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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.
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