title: Assessing tumor angiogenesis using macromolecular MR imaging contrast media.
abstract: MRI enhanced with a macromolecular contrast medium (MMCM) has previously been shown to estimate tumor microvascular characteristics that correlate closely with histologic microvascular density, an established surrogate of tumor angiogenesis. A similar MMCM-enhanced MRI technique has now been used to investigate the acute tumor microvascular effects of antibody-mediated inhibition of vascular endothelial growth factor (VEGF), a well-studied and potent angiogenesis stimulator. Athymic rats xenografted with a human breast carcinoma (MDA-MB-435) were imaged after administration of albumin-gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA30) using a heavily T1-weighted three dimensional-spoiled gradient-refocused acquisition in a steady-state pulse sequence before and 24 hours after treatment with anti-VEGF antibody (single dose of 1 mg). Changes in longitudinal relaxivity (delta R1) were analyzed using a bidirectional two-compartment kinetic model to estimate tumor fractional blood volume (fBV) and permeability surface area product (PS). Data showed a significant decrease (P < 0.05) of tumor PS with respect to macromolecular contrast medium at 24 hours after treatment with anti-VEGF antibody. No significant change was observed in fBV. Suppression of tumor microvascular permeability induced by anti-VEGF antibody can be detected and quantified by MMCM-enhanced MRI. MRI grading of tumor angiogenesis and monitoring of anti-angiogenesis interventions could find wide clinical application.
authors.affiliation: Department of Radiology, University of California San Francisco 94143-0628, USA.
authors.forename: R
authors.initials: R
authors.lastname: Brasch
authors.forename: C
authors.initials: C
authors.lastname: Pham
authors.forename: D
authors.initials: D
authors.lastname: Shames
authors.forename: T
authors.initials: T
authors.lastname: Roberts
authors.forename: K
authors.initials: K
authors.lastname: van Dijke
authors.forename: N
authors.initials: N
authors.lastname: van Bruggen
authors.forename: J
authors.initials: J
authors.lastname: Mann
authors.forename: S
authors.initials: S
authors.lastname: Ostrowitzki
authors.forename: O
authors.initials: O
authors.lastname: Melnyk
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D003937:Diagnosis, Differential; D016228:Endothelial Growth Factors / Q000032:analysis*; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009369:Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D051381:Rats; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D016228:Endothelial Growth Factors