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MRI monitoring of Avastin™ antiangiogenesis therapy using B22956/1, a new blood pool contrast agent, in an experimental model of human cancer

✍ Scribed by Anda Preda; Viktor Novikov; Martina Möglich; Karl Turetschek; David M. Shames; Robert C. Brasch; Friedrich M. Cavagna; Timothy P.L. Roberts


Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
476 KB
Volume
20
Category
Article
ISSN
1053-1807

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✦ Synopsis


Abstract

Purpose

To evaluate the diagnostic and prognostic potential of a new protein‐binding contrast medium, B22956/1, for quantitatively characterizing tumor microvessels by MRI and monitoring response to antiangiogenic therapy.

Materials and Methods

Dynamic contrast‐enhanced MRI (DCE‐MRI) was performed in an experimental cancer model with the use of the novel protein‐binding agent B22956/1, a low molecular contrast agent (ProHance™), and a macromolecular contrast medium, albumin‐(Gd‐DTPA). MDA‐MB‐435, a human cancer cell line, was implanted in 22 athymic rats. Animals were assigned randomly to a control (saline) or drug‐treated (Avastin™) group. MRI was performed at baseline and after nine days of treatment. The transendothelial permeability (K^PS^) and the fractional blood volume (fBV) were estimated from the kinetic analysis of dynamic MR data using a two‐compartment model. Tumor growth was also measured from volumetric MRI.

Results

Tumors grew more slowly, although not significantly (P = 0.07), in the drug‐treated group. The K^PS^ determined for B22956/1 decreased significantly in the drug‐treated group compared to baseline (P < 0.05), and progressed significantly in the control group. However, no significant changes were resolved with the use of ProHance or albumin‐(Gd‐DTPA).

Conclusion

With the use of appropriate contrast media, the therapeutic effects of an anti‐VEGF antibody on tumor microvessels can be monitored by dynamic MRI. The dynamic range of permeability to B22956/1, and the sensitivity to change of this parameter suggest a potential application in the clinical setting. J. Magn. Reson. Imaging 2004;20:865–873. © 2004 Wiley‐Liss, Inc.