411. Predicting Tumor Response to Oncolytic Virotherapy Using Dual Isotope SPECT/CT Imaging with NIS Reporter Gene and Duramycin

Abstract

Oncolytic virotherapy is a promising modality for cancer therapy and diverse viruses from various families have been genetically engineered to be tumor selective anticancer agents. To obtain an early readout on tumor susceptibility to the oncolytic virus, and potential toxicity from off target viral infection, we have engineered our oncolytic viruses to encode the thyroidal sodium iodide symporter gene (NIS) to enable noninvasive longitudinal imaging of the pharmacokinetics and sites of virus spread. The high resolution images obtained from the new generation of small animal SPECT/CT or PET/CT machines enable us to visualize increasing numbers of infectious foci daily within the subcutaneous tumors and to establish a mathematical model to develop strategies that will improve the outcome of virotherapy. In this study, we used the oncolytic Vesicular Stomatitis Virus (VSV) encoding NIS to evaluate the kinetics of intratumoral viral spread, and the subsequent aftermath of tumor cell death by apoptosis. Through I-125 SPECT/CT and NIS imaging, we showed rapid VSV spread within the susceptible MPC-11 murine plasmacytoma tumors, and the infectious foci grew larger and increased in numbers over 5 days. Since SPECT imaging enables concurrent dual isotope imaging, we also gave the same animal Tc-99m duramycin that detects apoptotic cells. In this MPC-11 model, we found rapid onset of apoptosis within the tumor. The infectious foci of viral infection (NIS imaging) and cell death (duramycin imaging) were coincident, overlapping at the acute phase of infection. In contrast, the CT-26 tumor was significantly less responsive to VSV-mIFN-NIS therapy, and there was minimal positive NIS signals or apoptosis. We are keen to further evaluate the potential of using dual isotope SPECT imaging using NIS reporter gene and the duramycin apoptosis tracer, with the goal of using this twin set of imaging methods to give us an early prediction of tumor response to oncolytic virotherapy.