Abstract #0919

Hyaluronan depletion improved intratumor pO2 and sensitized tumor to radiation therapy in pancreatic cancer model mouse.

Yu Saida¹, Tomohiro Seki², Shun Kishimoto¹, Yasunori Otowa¹, Kota Yamashita¹, Kazutoshi Yamamoto¹, Nallathamby Devasahayam¹, Jeffrey R. Brender¹, and Murali C. Krishna¹

¹Radiation Biology Branch, National Cancer Institute, Bethesda, MD, United States, ²Laboratory of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, Japan

PEGylated human hyaluronidase (PEGPH20) has been developed to enzymatically deplete tumor hyaluronan. The purpose of this study is to investigate physiologic and metabolic changes in pancreatic adenocarcinoma xenograft after PEGPH20 treatment by using multi-modal imaging and further determine the utility of PEGPH20 as radiosensitizer. PEGPH20 significantly increased intratumor pO₂ and blood volume and decreased glycolytic flux assessed by EPRI, USPIO-MRI, and hyperpolarized ¹³C-MRI, respectively. PEGPH20 also enhanced treatment effect of radiotherapy in vivo. The results validated the utility of the imaging methods to non-invasively monitor changes in the tumor microenvironment and predicted the radiosensitizing effect upon hyaluronan depletion.

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