Assessing tumor angiogenesis using macromolecular MR imaging contrast media.
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.
Brasch
R
R
Department of Radiology, University of California San Francisco 94143-0628, USA.
Pham
C
C
Shames
D
D
Roberts
T
T
van Dijke
K
K
van Bruggen
N
N
Mann
J
J
Ostrowitzki
S
S
Melnyk
O
O
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
D003287:Contrast Media; D016228:Endothelial Growth Factors