Diffusion-weighted and macromolecular contrast enhanced MRI of tumor response to antivascular therapy with ZD6126

The effects of the anti-vascular agent ZD6126 were studied in volume matched subcutaneous DU-145 human prostate cancer xenografts in SCID mice using two different MRI techniques, diffusion and vascular imaging. Diffusion weighted MRI was performed before and at 24 h, 48 h and 72 h following a single dose of 200 mg/kg. Tumor vascular volume and permeability surface area product (PSP) were determined 24 h post antivascular therapy following an identical dose using dynamic contrast enhanced MRI of the macromolecular contrast agent albumin-gadolinium diethylenetriaminepentaacetate (albumin-GdDTPA). Consistent with the mechanism of action of ZD6126, significantly lower vascular volume was detected at 24 h whereas diffusion changes were evident at 48 h. Diffusion MRI findings correlated well with histological determination of the necrotic fraction in the tumors by 48 h. Both diffusion and vascular imaging are useful noninvasive techniques to detect response of tumors to antivascular therapy with ZD6126 in the DU-145 human prostate cancer xenograft model.