Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging.

Abstract

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/mm(2)) and high b gradient values (ADC(high); b = 500, 750, and 1000 sec/mm(2)). 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 (R(2) = 0.46, P < .001) and the initial slope (R(2) = 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.

• Authors: Harriet C Thoeny, Frederik De Keyzer, Vincent Vandecaveye, Feng Chen, Xihe Sun, Hilde Bosmans, Robert Hermans, Eric K Verbeken, Chris Boesch, Guy Marchal, Willy Landuyt, Yicheng Ni
• Journal: Radiology (Radiology) Vol. 237 Issue 2 Pg. 492-9 (Nov 2005) ISSN: 0033-8419 [Print] United States
• PMID: 16192323 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Contrast Media
• Stilbenes
• gadodiamide
• fosbretabulin
• Gadolinium DTPA

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics)
• Contrast Media
• Diffusion Magnetic Resonance Imaging
• Gadolinium DTPA
• Image Processing, Computer-Assisted
• Injections, Intraperitoneal
• Linear Models
• Magnetic Resonance Imaging
• Male
• Rats
• Rats, Inbred Strains
• Rhabdomyosarcoma (blood supply)
• Soft Tissue Neoplasms (blood supply)
• Stilbenes (administration & dosage, pharmacokinetics)