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Effect of Vascular Targeting Agent in Rat Tumor Model: Dynamic Contrast-enhanced versus Diffusion-weighted MR Imaging¹

¹ From the Departments of Radiology (H.C.T., F.D.K., V.V., F.C., X.S., H.B., R.H., G.M., Y.N.) and Pathology (E.K.V.), University Hospitals Leuven, Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium; Departments of Diagnostic, Interventional and Pediatric Radiology (H.C.T.) and Clinical Research (C.B.), University Hospital of Bern, Inselspital, Bern, Switzerland; and Laboratory of Experimental Radiobiology/LEO, Catholic University Leuven, Leuven, Belgium (W.L.). Received September 23, 2004; revision requested November 26; revision received January 12, 2005; accepted February 1. H.C.T. supported by a grant from the Bernese Cancer League and by the Kurt and Senta Hermann Foundation. Address correspondence to R.H. (e-mail: robert.hermans{at}uz.kuleuven.ac.be).

PURPOSE: To compare dynamic contrast material–enhanced magnetic resonance (MR) imaging and diffusion-weighted MR imaging for noninvasive evaluation of early and late effects of a vascular targeting agent in a rat tumor model.

MATERIALS AND METHODS: The study protocol was approved by the local ethics committee for animal care and use. Thirteen rats with one rhabdomyosarcoma in each flank (26 tumors) underwent dynamic contrast-enhanced imaging and diffusion-weighted echo-planar imaging in a 1.5-T MR unit before intraperitoneal injection of combretastatin A4 phosphate and at early (1 and 6 hours) and later (2 and 9 days) follow-up examinations after the injection. Histopathologic examination was performed at each time point. The apparent diffusion coefficient (ADC) of each tumor was calculated separately on the basis of diffusion-weighted images obtained with low b gradient values (ADC_low; b = 0, 50, and 100 sec/mm²) and high b gradient values (ADC_high; b = 500, 750, and 1000 sec/mm²). The difference between ADC_low and ADC_high was used as a surrogate measure of tissue perfusion (ADC_low – ADC_high = ADC_perf). From the dynamic contrast-enhanced MR images, the volume transfer constant k and the initial slope of the contrast enhancement–time curve were calculated. For statistical analyses, a paired two-tailed Student t test and linear regression analysis were used.

RESULTS: Early after administration of combretastatin, all perfusion-related parameters (k, initial slope, and ADC_perf) decreased significantly (P < .001); at 9 days after combretastatin administration, they increased significantly (P < .001). Changes in ADC_perf were correlated with changes in k (R² = 0.46, P < .001) and the initial slope (R² = 0.67, P < .001).

CONCLUSION: Both dynamic contrast-enhanced MR imaging and diffusion-weighted MR imaging allow monitoring of perfusion changes induced by vascular targeting agents in tumors. Diffusion-weighted imaging provides additional information about intratumoral cell viability versus necrosis after administration of combretastatin.

© RSNA, 2005

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