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


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 (KPS) 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 KPS 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).


CONCLUSIONS
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.
Preda
Anda
A
Center for Pharmaceutical and Molecular Imaging, Department of Radiology, University of California-San Francisco, San Francisco, California, USA.
Novikov
Viktor
V
Möglich
Martina
M
Turetschek
Karl
K
Shames
David M
DM
Brasch
Robert C
RC
Cavagna
Friedrich M
FM
Roberts
Timothy P L
TP
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000098:blood supply* / Q000175:diagnosis*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009942:Organometallic Compounds; D051381:Rats; D011923:Rats, Nude
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C440468:B-22956-1; D003287:Contrast Media; D009942:Organometallic Compounds; D000068258:Bevacizumab; D019786:Gadolinium DTPA