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

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

Research output: Contribution to journalArticle

52 Citations (Scopus)

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 virusinfected 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-tonormal 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.

Original languageEnglish (US)
Pages (from-to)553-561
Number of pages9
JournalMolecular Therapy
Volume10
Issue number3
DOIs
StatePublished - Sep 2004
Externally publishedYes

Fingerprint

Oncolytic Viruses
Somatostatin Receptors
Molecular Imaging
Vaccinia virus
Neoplasms
Radioactivity
Injections
somatostatin receptor 2
pentetreotide
Somatostatin
Transgenes
Reporter Genes
Heterografts
Nude Mice
Genetic Therapy
Colon
Clinical Trials
Viruses

Keywords

  • Gene therapy
  • Molecular imaging
  • Reporter genes
  • Somatostatin receptor
  • Vaccinia virus

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2 : Molecular imaging after systemic delivery using 111In-pentetreotide. / McCart, J. Andrea; Mehta, Navneet; Scollard, Deborah; Reilly, Raymond M.; Carrasquillo, Jorge A.; Tang, Nan; Deng, Hui; Miller, Marshall; Xu, Hui; Libutti, Steven K.; Alexander, H. Richard; Bartlett, David L.

In: Molecular Therapy, Vol. 10, No. 3, 09.2004, p. 553-561.

Research output: Contribution to journalArticle

McCart, JA, Mehta, N, Scollard, D, Reilly, RM, Carrasquillo, JA, Tang, N, Deng, H, Miller, M, Xu, H, Libutti, SK, Alexander, HR & Bartlett, DL 2004, 'Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2: Molecular imaging after systemic delivery using 111In-pentetreotide', Molecular Therapy, vol. 10, no. 3, pp. 553-561. https://doi.org/10.1016/j.ymthe.2004.06.158
McCart, J. Andrea ; Mehta, Navneet ; Scollard, Deborah ; Reilly, Raymond M. ; Carrasquillo, Jorge A. ; Tang, Nan ; Deng, Hui ; Miller, Marshall ; Xu, Hui ; Libutti, Steven K. ; Alexander, H. Richard ; Bartlett, David L. / Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2 : Molecular imaging after systemic delivery using 111In-pentetreotide. In: Molecular Therapy. 2004 ; Vol. 10, No. 3. pp. 553-561.
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