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Low-molecular contrast agent dynamic contrast-enhanced (DCE)-MRI and diffusion-weighted (DW)-MRI in early assessment of bevacizumab treatment in breast cancer xenografts.
Moestue, Siver A. PhD 1; Huuse, Else M. PhD 1; Lindholm, Evita M. MSc 2; Bofin, Anna MD, PhD 3; Engebraaten, Olav MD, PhD 2,4; Maelandsmo, Gunhild M. PhD 2,5; Akslen, Lars A. MD, PhD 6; Gribbestad, Ingrid S. PhD 1
[Article] Journal of Magnetic Resonance Imaging. 38(5):1043-1053, November 2013.

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Purpose: To investigate the effect of bevacizumab treatment on vascular architecture and function in two xenograft models with different angiogenic properties using diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI).

Materials and Methods: Mice carrying basal-like (MAS98.12) or luminal-like (MAS98.06) orthotopic breast cancer xenografts were treated with bevacizumab (5 mg/kg), doxorubicin (8 mg/kg), or both drugs in combination. DW-MRI and DCE-MRI were performed before and 3 days after treatment using a Bruker 7T preclinical scanner. Mean microvessel density (MVD) and proliferating microvessel density (pMVD) in the tumors were determined for evaluation of vascular response to bevacizumab treatment.

Results: No changes in DCE-MRI or DW-MRI parameters were observed in untreated controls during the experiment period. DW-MRI showed increased apparent diffusion coefficient (ADC) values in all treatment groups in both basal-like and luminal-like xenografts. DCE-MRI showed increased contrast agent uptake, particularly in central regions of the tumors, after bevacizumab/combination treatment in both xenograft models. This was accompanied by decreased MVD and pMVD in basal-like xenografts. Doxorubicin treatment had no effect on DCE-MRI parameters in any of the xenograft models.

Conclusion: Both DW-MRI and DCE-MRI demonstrated an early response to bevacizumab treatment in the xenograft tumors. Increased contrast agent uptake and reduced MVD/pMVD is consistent with a normalization of vascular function. J. Magn. Reson. Imaging 2013;38:1043-1053. (C) 2013 Wiley Periodicals, Inc.