Hans-Juergen Raatschen MD, Presenter: Nothing to Disclose

Yanjun Fu PhD, Abstract Co-Author: Nothing to Disclose

David M Shames MD, Abstract Co-Author: Nothing to Disclose

Robert Charles Brasch MD, Abstract Co-Author: Nothing to Disclose

To determine if the change in MRI-assayed tumor vascular leakiness after a single dose of angiogenesis inhibitor, bevacizumab (Avastin™) can serve as a biomarker for delayed tumor growth response.

MDA-MB 435 breast cancer cells were injected subcutaneously in 15 female nude rats for tumor induction. When tumors reached a diameter of 1 cm, albumin-(Gd-DTPA)-enhanced dynamic MRI was performed. Immediately after baseline imaging, angiogenesis inhibition was initiated with doses given every third day for a total of four doses by i.p. injection of the human anti-VEGF antibody bevacizumab (Avastin™) at three different dose levels: 0.1 mg (n=3), 0.5mg (n=5) and 1.0 mg (n=3). The control animals (n=4) received an i.p. injection of saline. The second MRI was performed 24 hours after treatment initiation. Baseline and post-treatment tumor vascular leakiness expressed as the endothelial transfer coefficient KPS was calculated and the difference was expressed as percentage of KPS change. Tumor volume was measured every second day by caliper and tumor growth rate was determined by monoexponential data fitting.

The MRI-assayed tumor microvascular leakiness, used as a biomarker, showed a positive and significant correlation with tumor growth rate (r2=0.75, pPS showed an increase of 23% in the control group and decreased significantly (p < 0.05) in the three different Avastin-treated groups 24 hours after a single injection of bevacizumab: -62 % (0.1 mg group), -88% (0.5 mg group) and -95% (1.0 mg group). After 10 days of Avastin treatment, the 0.5 and 1.0 mg groups showed a significantly (p < 0.05) slower tumor growth rate (0.12 ± 0.01 and 0.14 ± 0.02, respectively) than the control group (0.2 ± 0.03).

The dynamic MRI-assayed tumor response to the angiogenesis inhibitor Avastin™, reflected in the suppression of vascular leakiness 24 hours after a single dose was strongly correlated with tumor growth suppression at 10 days of treatment and thus was a successful biomarker.

MRI-assayed tumor vascular leakiness can serve as a biomarker for tumor growth response to angiogenesis inhibtion.

Raatschen, H, Fu, Y, Shames, D, Brasch, R, MR Imaging is a Biomarker for Tumor Angiogenesis Response to Avastin™.  Radiological Society of North America 2006 Scientific Assembly and Annual Meeting, November 26 - December 1, 2006 ,Chicago IL. http://archive.rsna.org/2006/4427504.html