Early effects of low dose bevacizumab treatment assessed by magnetic resonance imaging

BACKGROUND: Antiangiogenic treatments have been shown to increase blood perfusion and oxygenation in some experimental tumors, and to reduce blood perfusion and induce hypoxia in others. The purpose of this preclinical study was to investigate the potential of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted MRI (DW-MRI) in assessing early effects of low dose bevacizumab treatment, and to investigate intratumor heterogeneity in this effect. METHODS: A-07 and R-18 human melanoma xenografts, showing high and low expression of VEGF-A, respectively, were used as tumor models. Untreated and bevacizumab-treated tumors were subjected to DCE-MRI and DW-MRI before treatment, and twice during a 7-days treatment period. Tumor images of K(trans) (the volume transfer constant of Gd-DOTA) and v(e) (the fractional distribution volume of Gd-DOTA) were produced by pharmacokinetic analysis of the DCE-MRI data, and tumor images of ADC (the apparent diffusion coefficient) were produced from DW-MRI data. RESULTS: Untreated A-07 tumors showed higher K(trans), v(e), and ADC values than untreated R-18 tumors. Untreated tumors showed radial heterogeneity in K(trans), i.e., K(trans) was low in central tumor regions and increased gradually towards the tumor periphery. After the treatment, bevacizumab-treated A-07 tumors showed lower K(trans) values than untreated A-07 tumors. Peripherial tumor regions showed substantial reductions in K(trans), whereas little or no effect was seen in central regions. Consequently, the treatment altered the radial heterogeneity in K(trans). In R-18 tumors, significant changes in K(trans) were not observed. Treatment induced changes in tumor size, v(e), and ADC were not seen in any of the tumor lines. CONCLUSIONS: Early effects of low dose bevacizumab treatment may be highly heterogeneous within tumors and can be detected with DCE-MRI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1918-1) contains supplementary material, which is available to authorized users.