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

BMC Cancer

Research Article

Lise Mari K. Andersen¹  Trude G. Simonsen¹  Ragnhild Smistad¹  Catherine S. Wegner¹  Jon-Vidar Gaustad¹  Einar K. Rofstad¹ 

[1] Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway;

关键词: Bevacizumab;    Antiangiogenic treatment;    Blood perfusion;    Intratumor heterogeneity;    DCE-MRI;    DW-MRI;   

DOI  :  10.1186/s12885-015-1918-1

 received in 2015-08-04, accepted in 2015-11-06,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundAntiangiogenic 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.MethodsA-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 Ktrans (the volume transfer constant of Gd-DOTA) and ve (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.ResultsUntreated A-07 tumors showed higher Ktrans, ve, and ADC values than untreated R-18 tumors. Untreated tumors showed radial heterogeneity in Ktrans, i.e., Ktrans was low in central tumor regions and increased gradually towards the tumor periphery. After the treatment, bevacizumab-treated A-07 tumors showed lower Ktrans values than untreated A-07 tumors. Peripherial tumor regions showed substantial reductions in Ktrans, whereas little or no effect was seen in central regions. Consequently, the treatment altered the radial heterogeneity in Ktrans. In R-18 tumors, significant changes in Ktrans were not observed. Treatment induced changes in tumor size, ve, and ADC were not seen in any of the tumor lines.ConclusionsEarly effects of low dose bevacizumab treatment may be highly heterogeneous within tumors and can be detected with DCE-MRI.

【 授权许可】

CC BY   
© Gaustad et al. 2015

【 图 表 】

Fig. 1