Bortezomib Treatment Reduces Tumor Blood Flow and Perfusion as Measured by Dynamic Contrast-Enhanced 1H MRI

Ellen Ackerstaff¹, Xiaorong Sun^1,2, Mihai Coman (Deceased)¹, Ya Wang¹, Hung Tsung Hsiao¹, Fuqiu He¹, Ligang Xing^1,2, Sean Carlin¹, C Clifton Ling¹, Jason A. Koutcher¹, Gloria C. Li¹

The proteasomes inhibitor Bortezomib possesses anti-angiogenic and anti-tumor properties and appears to selectively interfere in the hypoxia pathway. Our study aims to determine biomarkers characterizing treatment response. We studied in a colorectal cancer model the effects of Bortezomib on the tumor vasculature by in vivo DCE MRI and on the tumor hypoxia response ex vivo using immunohistochemistry. Our data suggest that Bortezomib treatment modifies the tumor microenvironment by decreasing tumor perfusion. Our ex vivo data indicate a reduced hypoxia response in central regions of the tumor and an increased hypoxia response in the tumor rim in response to Bortezomib treatment.