title: Characterization of bevacizumab dose response relationship in U87 brain tumors using magnetic resonance imaging measures of enhancing tumor volume and relative cerebral blood volume.
abstract: Despite the early promising results with the anti-angiogenic agent, bevacizumab, to prolong time to progression in patients with brain tumors, the optimal dose and drug combinations have not yet been defined. The purpose of this study was to characterize the bevacizumab dose-response relationship for brain tumors by measuring the contrast-agent enhanced tumor volumes and relative cerebral blood volume (rCBV) using dynamic susceptibility contrast (DSC) imaging. The studies, performed in the U87 brain tumor model using doses of bevacizumab ranging from 0 to 10 mg/kg, demonstrate that tumor growth and vascularity are inhibited at all doses used, compared to untreated controls. However, only the maximum dose showed a statistically significant difference in growth rate. Conversely tumor vascularity, as measured with rCBV, was inhibited equally well for all doses used with no clear indication that higher doses are more effective.
authors.affiliation: Translational Brain Tumor Program, Medical College of Wisconsin, Milwaukee, WI, USA. kpechman@mcw.edu
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Pechman
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Donohoe
authors.forename: Devyani P
authors.initials: DP
authors.lastname: Bedekar
authors.forename: Shekar N
authors.initials: SN
authors.lastname: Kurpad
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Hoffmann
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Schmainda
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001810:Blood Volume; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D003287:Contrast Media; D004305:Dose-Response Relationship, Drug; D019786:Gadolinium DTPA; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000068258:Bevacizumab; D019786:Gadolinium DTPA