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McCart, J.A. et al.

McCart, Mehta, Scollard, Reilly, Carrasquillo, Tang, Deng, Miller, Xu, Libutti, Alexander, Bartlett,

Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2: molecular imaging after systemic delivery using 111In-pentetreotide.

Oncolytic vaccinia viruses (VV) have demonstrated tumor specificity, high levels of transgene expression, and anti-tumor effects. The ability to visualize vector biodistribution noninvasively will be necessary as gene therapy vectors come to clinical trials, and the creation of a VV that can both treat tumors and permit noninvasive imaging after systemic delivery is therefore an exciting concept. To facilitate imaging, a VV expressing the human somatostatin receptor type 2 ( SSTR2) was created. Cells infected with the SSTR2- expressing VV or controls were incubated with the somatostatin analog 111In-pentetreotide with or without an excess of nonradiolabeled pentetreotide. The SSTR2-infected cells bound 111In-pentetreotide sixfold more efficiently than control virus-infected cells and this binding was specifically blocked by nonradiolabeled pentetreotide. Nude mice bearing subcutaneous murine colon CA xenografts were injected intraperitoneally with the SSTR2-expressing VV or control VV. After 6 days, mice were injected with 111In-pentetreotide and imaged. Mice were sacrificed and organs collected and counted in a gamma counter. The uptake of radioactivity in tumors and normal tissues (percentage injected dose per gram) and tumor-to-normal tissue ratios were determined. Tumors infected with the SSTR2-expressing VV accumulated significantly higher concentrations of radioactivity compared to tumors in animals receiving the control virus. SSTR2-infected tumors were visible on imaging 6 days after VV injection and could be visualized for up to 3 weeks post-viral injection using repeat injections of 111In-pentetreotide. This reporter gene imaging strategy could be a very effective method to visualize vector distribution, expression, and persistence over time and enhances the potential of VV as a novel anti-cancer therapeutic.[1]

References

Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2: molecular imaging after systemic delivery using 111In-pentetreotide. McCart, J.A., Mehta, N., Scollard, D., Reilly, R.M., Carrasquillo, J.A., Tang, N., Deng, H., Miller, M., Xu, H., Libutti, S.K., Alexander, H.R., Bartlett, D.L. Mol. Ther. (2004) [Pubmed]

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