Abstract
Abstract RATIONALE: The inability to deliver viruses homogeneously throughout solid tumors is a universal obstacle encountered in oncolytic virotherapy. The initial intratumoral viral dispersion volume is a critical determinant of virotherapy efficacy, and depends not only on the number of infected cells, but also on the spatial distribution of the infected cells. In this study, we determined the feasibility and usefulness of monitoring the initial intratumoral delivery of oncolytic viruses to solid tumors using contrast-enhanced computed tomography (CT). EXPERIMENTAL PROCEDURES: Human BxPC-3 pancreatic tumor xenografts were established in nude mice. An engineered oncolytic measles virus expressing the sodium iodide symporter reporter (MV-NIS) was mixed with a 1:10 dilution of Omnipaque-300 contrast material and injected directly into mouse tumors. Mice were imaged with micro-CT immediately pre and post-injection of the virus + Omnipaque solution and on day 3 post-injection with 99mTcO4 micro-SPECT/CT. Tumors were harvested immediately after micro-SPECT/CT imaging for autoradiography and immunistochemistry analysis of radioactivity uptake and viral infection. Linear regression and Spearman correlation analyses were performed to determine the relationship between intratumoral contrast enhancement and subsequent intratumoral viral infection. RESULTS: This dilution of Omnipaque was found to have no effect on viral infectivity or cell viability in vitro, yet was more than adequate for CT imaging of the virus + Omnipaque injectate distribution following intratumoral injection. Ex vivo autoradiography and immunohistochemistry confirmed a strong correlation between intratumoral CT contrast enhancement, SPECT activity, viral infection, and sodium iodide symporter activity. CONCLUSIONS: This injection method is translatable to the clinic and should allow optimization of intratumoral injection in humans. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4145. doi:10.1158/1538-7445.AM2011-4145
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call