title: Dynamic MRI using iron oxide nanoparticles to assess early vascular effects of antiangiogenic versus corticosteroid treatment in a glioma model.
abstract: 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.affiliation: Department of Neuroradiology, Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: Csanad G
authors.initials: CG
authors.lastname: Varallyay
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Muldoon
authors.forename: Seymur
authors.initials: S
authors.lastname: Gahramanov
authors.forename: Yingjen J
authors.initials: YJ
authors.lastname: Wu
authors.forename: James A
authors.initials: JA
authors.lastname: Goodman
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Martin M
authors.initials: MM
authors.lastname: Pike
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002199:Capillary Permeability; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D016903:Drug Monitoring / Q000379:methods; D005290:Ferric Compounds; D019786:Gadolinium DTPA; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles; D051381:Rats
chemical_list: D000305:Adrenal Cortex Hormones; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005290:Ferric Compounds; C000499:ferric oxide; D000068258:Bevacizumab; D003907:Dexamethasone; C064925:gadodiamide; D019786:Gadolinium DTPA