Seung Hong Choi MD, PhD, Presenter: Nothing to Disclose

Tumor-associated macrophages (TAMs) have long been considered capable of destroying tumor cells and presenting tumor antigens to effector T cells to trigger antitumor responses. Recently, several studies have shown that TAM recruitment to the cancer site increases tumor angiogenesis as well as tumor cell migration, invasion and dissemination and that TAMs also suppress the immune response that targets tumor cells. Dynamic susceptibility contrast (DSC) MR imaging is advanced technique that provides cerebral blood volume (CBV) and can be used for the assessment of tumor response to therapy, especially for antiangiogenic therapy such as bevacizumab. The purpose of the present study is to investigate whether the recruitment of CCL2-dependent macrophage decreases response to antiangiogenic treatment by using DSC perfusion MR Imaging and microvessel density (MVD) measurement in a rat glioblastoma model.

We established U87 human glioblastoma cell line expressing macrophage chemoattractant CCL2, and confirmed the CCL2 expression by western blot and cytokine assay. For in vivo study, athymic nude rats were used for orthotopic brain tumor model (control (n = 6), and CCL2 group (n = 6), respectively). And then 2 weeks after transplantation, DSC MR imaging was performed with 9.4T animal MR scanner for pre-treatment MR imaging. Bevacizumab (20 mg/kg) was intra-peritoneally injected twice a week, then post-treatment MR imaging was performed. After sacrifice of the rats, MVD was determined by CD34, and macrophages were stained with CD68.

CCL2 expressing tumors showed significantly higher relative CBV than mock-transfected controls after treatment of bevacizumab (3.5 ± 1.2 vs 1.3 ± 0.4, P ≤ 0.05). In histology analysis, more MVD formatted by bevacizumab resistance and more macrophages recruited by CCL2 cytokine were observed in CCL2 expressing tumor than mock-transfected control tumors after treatment of bevacizumab. 

We believe that CCL2 expression of glioblastoma can induce the antiangiogenic drug resistance by recruitment of macrophages, which can be assessed noninvasively with DSC MR imaging. 

DSC imaging can be used for the noninvasive evaluation of the resistance to antiangiogenic treatment in the preclinical study. 

Choi, S, Recruitment of CCL2-dependent Macrophage Decreases Response to Antiangiogenic Treatment: Preliminary Study Using Dynamic Susceptibility Contrast Perfusion MR Imaging and Microvessel Density Measurement in a Rat Glioblastoma Model.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14006925.html