PEGylated human hyaluronidase (PEGPH20) enzymatically deplete tumor hyaluronan, and allows re-expansion of intra-tumor vasculature to increase the delivery of therapeutic molecules. The purpose of this study was to monitor physiologic and metabolic changes in pancreatic adenocarcinoma xenograft in response to PEGPH20 treatment by using multi-modal imaging methods including hyperpolarized 13C-MRI with [1-13C] pyruvate, EPRI, DCE-MRI, and photoacoustic imaging. Significantly decreased glycolysis, increased intratumor pO2, improved perfusion, and increased oxyhemoglobin saturation as well as increased blood volume, were observed after PEGPH20 treatment. The results validate the utility of these imaging methods to non-invasively monitor the PEGPH20-induced changes in the tumor microenvironment.
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