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Abstract #3429

Multimodal molecular imaging assessment of tumor microenvironment. Hyaluronan depletion induces tumor reoxygenation and radiosensitization

Shun C Kishimoto1, Tomohiro Seki2, Yu Saida3, Yasunori Otowa1, Kota Yamashita1, Kazutoshi Yamamoto1, Nallathamby Devasahayam1, Jeffrey R Brender1, and Murali C Krishna1
1NCI, Bethesda, MD, United States, 2Josai University, Sakado, Japan, 3Medical and Dental Hospital, Niigata University, Niigata, Japan

Synopsis

PEGPH20 is a PEGylated form of recombinant human hyaluronidase PH20. The purpose of this study is to investigate physiologic changes in pancreatic adenocarcinoma xenograft after PEGPH20 treatment using multi-modal imaging and further determine the utility of PEGPH20 as radiosensitizer. PEGPH20 treatment significantly increased intratumor pO2, blood perfusion and volume, and decreased glycolytic flux assessed by EPR, MRI with USPIO or Gd, and 13C DNP MRI, respectively. PEGPH20 enhanced treatment effect of radiotherapy. The results validated the utility of the imaging methods to monitor the changes in the tumor microenvironment after hyaluronan depletion and to predict the radio-sensitizing effect of PEGPH20.

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Keywords