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


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).


CONCLUSIONS
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.
Thoeny
Harriet C
HC
Department of Radiology and Pathology, University Hospitals Leuven, 3000 Leuven, Belgium.
De Keyzer
Frederik
F
Vandecaveye
Vincent
V
Chen
Feng
F
Sun
Xihe
X
Bosmans
Hilde
H
Hermans
Robert
R
Verbeken
Eric K
EK
Boesch
Chris
C
Marchal
Guy
G
Landuyt
Willy
W
Ni
Yicheng
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003287:Contrast Media; D038524:Diffusion Magnetic Resonance Imaging; D019786:Gadolinium DTPA; D007091:Image Processing, Computer-Assisted; D007274:Injections, Intraperitoneal; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012208:Rhabdomyosarcoma / Q000098:blood supply*; D012983:Soft Tissue Neoplasms / Q000098:blood supply*; D013267:Stilbenes / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D013267:Stilbenes; C064925:gadodiamide; C058728:fosbretabulin; D019786:Gadolinium DTPA