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

Abstract

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.

• Authors: J Andrea McCart, Navneet Mehta, Deborah Scollard, Raymond M Reilly, Jorge A Carrasquillo, Nan Tang, Hui Deng, Marshall Miller, Hui Xu, Steven K Libutti, H Richard Alexander, David L Bartlett
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 10 Issue 3 Pg. 553-61 (Sep 2004) ISSN: 1525-0016 [Print] United States
• PMID: 15336655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indium Radioisotopes
• Receptors, Somatostatin
• Somatostatin
• somatostatin receptor 2
• pentetreotide

Topics

• Animals
• Colonic Neoplasms (diagnostic imaging, metabolism)
• Female
• Genetic Vectors (pharmacokinetics)
• Haplorhini
• Humans
• Indium Radioisotopes (chemistry, pharmacokinetics)
• Mice
• Mice, Nude
• Radionuclide Imaging
• Receptors, Somatostatin (biosynthesis, genetics)
• Somatostatin (analogs & derivatives, chemistry, pharmacokinetics)
• Tissue Distribution
• Transplantation, Heterologous
• Tumor Cells, Cultured
• Vaccinia virus (chemistry, genetics, metabolism)