Estimating human glioblastoma xenograft DCE-MRI response to Bevacizumab treatment

Abstract

Background and purpose: It has been suggested that consecutive DCE-MRI in the early phase of treatment with bevacizumab could provide a better estimate of treatment response. Materials and methods: The xenograft study was performed using adult (8-12 weeks of age) male type NMRINUM Mice (Taconic, Denmark). A human glioblastoma xenograft was inoculated subcutaneously in the posterior flank of the mouse. DCE MRI and compartment analysis was performed extended Toft´s model. Pathology immunohistochemistry of Glial fibrillary acidic protein (GFAP) of excised tumors slides were analyzed using an ImageJ threshold watershed technique to determine tissue fraction of glial tumor cells. Results: A total of 15 intervention tumors and two C16MG control tumors were subjected to DCE MRI. A significant correlation between Ktrans and GFAP was observed. Furthermore a significant reduction in Ktrans following Bevacizumab was observed. Conclusion: To conclude this study successfully established a technique, which allowed small animals with Xenograft heterotopic implanted GBM tumors to be scanned with a DCE-MRI technique using a clinical 3T MR scanner setting. Furthermore the Ktrans parameters derived was demonstrated to be a potential imaging biomarker of GBM GFAP activity and treatment response to Bevacizumab.