O'Hara, J. A., Blumenthal, R. D., Grinberg, O. Y., Demidenko, E., Grinberg, S., Wilmot, C. M., Taylor, A. M., Goldenberg, D. M. and Swartz, H. M. Response to Radioimmunotherapy Correlates with Tumor pO₂ Measured by EPR Oximetry in Human Tumor Xenografts.

The efficacy of radiation treatment depends upon local oxygen concentration. We postulated that the variability in responsiveness of tumor xenografts to a fixed dose of radioimmunotherapy might be related to the tumor pO₂ at the time that radioimmunotherapy was administered. We evaluated the growth of xenografts of CALU-3 tumors, a non-small cell lung carcinoma, in response to an 8.9-MBq dose of ¹³¹I-RS-7-anti-EGP-1 and correlated tumor growth rate with initial tumor pO₂ measured by EPR oximetry. The greatest growth delay in response to radioimmunotherapy had the highest initial pO₂, and the fastest-growing tumors had the lowest initial pO₂. We then determined the dynamic effect of radioimmunotherapy on tumor pO₂ by serial measurements of pO₂ for 35 days after radioimmunotherapy. This information could be important for ascertaining the likelihood that a tumor will respond to additional doses as part of a multiple dose scheme. Serial tumor pO₂ measurements may help identify a window of opportunity when the surviving tumor regions will be responsive to a second round of radioimmunotherapy or a second therapeutic modality such as chemotherapy or an anti-vascular agent. After radioimmunotherapy, there was an increase in tumor pO₂ followed by a decrease below initial levels in most mice. Thus defined times may exist when a tumor is more or less radiosensitive after radioimmunotherapy.