Quantitative molecular imaging of viral therapy for pancreatic cancer using an engineered measles virus expressing the sodium-iodide symporter reporter gene

Stephanie K Carlson, Kelly L. Classic, Elizabeth M. Hadac, David M Dingli, Claire E. Bender, Bradley J. Kemp, Stephen J Russell

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

OBJECTIVE. Our objectives were to, first, determine the oncolytic potential of an engineered measles virus expressing the sodium-iodide symporter gene (MV-NIS) for intratumoral (IT) therapy of pancreatic cancer and, second, evaluate NIS as a reporter gene for in vivo monitoring and quantitation of MV-NIS delivery, viral spread, and gene expression in this tumor model. MATERIALS AND METHODS. Cultured human pancreatic cancer cells were infected with MV-NIS. Light microscopy, cell viability, and iodide uptake assays were used to confirm viral infection and NIS gene expression and function in vitro. Human pancreatic tumor xenografts were established in mice and infected via IT MV-NIS injections. NIS-mediated IT iodide uptake was quantitated by 123I micro-SPECT/CT. IT MV-NIS infection was confirmed by immunohistochemistry of excised pancreatic xenografts. The oncolytic efficacy of MV-NIS was determined by measurement of tumor growth and mouse survival. RESULTS. Infection of human pancreatic cancer cell lines with MV-NIS in vitro resulted in syncytia formation, marked iodide uptake, and ultimately cell death. Tumor xenografts infected with MV-NIS concentrated radioiodine, allowing serial quantitative imaging with 123I micro-SPECT/CT. IT MV-NIS therapy of human pancreatic cancer xenografts resulted in a significant reduction in tumor volume and increased survival time of the treated mice compared with the control mice. CONCLUSION. MV-NIS efficiently infects human pancreatic tumor cells and results in sufficient radioiodine uptake to enable noninvasive serial imaging and quantitation of the intensity, distribution, and time course of NIS gene expression. MV-NIS also shows oncolytic activity in human pancreatic cancer xenografts: Tumor growth is reduced and survival is increased in mice treated with the virus.

Original languageEnglish (US)
Pages (from-to)279-287
Number of pages9
JournalAmerican Journal of Roentgenology
Volume192
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Measles virus
Molecular Imaging
Pancreatic Neoplasms
Reporter Genes
Heterografts
Iodides
Neoplasms
Gene Expression
Therapeutics
Survival
Viral Genes
Virus Diseases
Giant Cells
Growth
Infection
Tumor Burden
Human Activities
sodium-iodide symporter
Microscopy
Cell Survival

Keywords

  • Gene therapy
  • Measles virus
  • Micro-SPECT/CT
  • Molecular imaging
  • Pancreatic cancer
  • Sodium-iodide symporter
  • Viral therapy

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Quantitative molecular imaging of viral therapy for pancreatic cancer using an engineered measles virus expressing the sodium-iodide symporter reporter gene. / Carlson, Stephanie K; Classic, Kelly L.; Hadac, Elizabeth M.; Dingli, David M; Bender, Claire E.; Kemp, Bradley J.; Russell, Stephen J.

In: American Journal of Roentgenology, Vol. 192, No. 1, 01.2009, p. 279-287.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVE. Our objectives were to, first, determine the oncolytic potential of an engineered measles virus expressing the sodium-iodide symporter gene (MV-NIS) for intratumoral (IT) therapy of pancreatic cancer and, second, evaluate NIS as a reporter gene for in vivo monitoring and quantitation of MV-NIS delivery, viral spread, and gene expression in this tumor model. MATERIALS AND METHODS. Cultured human pancreatic cancer cells were infected with MV-NIS. Light microscopy, cell viability, and iodide uptake assays were used to confirm viral infection and NIS gene expression and function in vitro. Human pancreatic tumor xenografts were established in mice and infected via IT MV-NIS injections. NIS-mediated IT iodide uptake was quantitated by 123I micro-SPECT/CT. IT MV-NIS infection was confirmed by immunohistochemistry of excised pancreatic xenografts. The oncolytic efficacy of MV-NIS was determined by measurement of tumor growth and mouse survival. RESULTS. Infection of human pancreatic cancer cell lines with MV-NIS in vitro resulted in syncytia formation, marked iodide uptake, and ultimately cell death. Tumor xenografts infected with MV-NIS concentrated radioiodine, allowing serial quantitative imaging with 123I micro-SPECT/CT. IT MV-NIS therapy of human pancreatic cancer xenografts resulted in a significant reduction in tumor volume and increased survival time of the treated mice compared with the control mice. CONCLUSION. MV-NIS efficiently infects human pancreatic tumor cells and results in sufficient radioiodine uptake to enable noninvasive serial imaging and quantitation of the intensity, distribution, and time course of NIS gene expression. MV-NIS also shows oncolytic activity in human pancreatic cancer xenografts: Tumor growth is reduced and survival is increased in mice treated with the virus.",
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T1 - Quantitative molecular imaging of viral therapy for pancreatic cancer using an engineered measles virus expressing the sodium-iodide symporter reporter gene

AU - Carlson, Stephanie K

AU - Classic, Kelly L.

AU - Hadac, Elizabeth M.

AU - Dingli, David M

AU - Bender, Claire E.

AU - Kemp, Bradley J.

AU - Russell, Stephen J

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N2 - OBJECTIVE. Our objectives were to, first, determine the oncolytic potential of an engineered measles virus expressing the sodium-iodide symporter gene (MV-NIS) for intratumoral (IT) therapy of pancreatic cancer and, second, evaluate NIS as a reporter gene for in vivo monitoring and quantitation of MV-NIS delivery, viral spread, and gene expression in this tumor model. MATERIALS AND METHODS. Cultured human pancreatic cancer cells were infected with MV-NIS. Light microscopy, cell viability, and iodide uptake assays were used to confirm viral infection and NIS gene expression and function in vitro. Human pancreatic tumor xenografts were established in mice and infected via IT MV-NIS injections. NIS-mediated IT iodide uptake was quantitated by 123I micro-SPECT/CT. IT MV-NIS infection was confirmed by immunohistochemistry of excised pancreatic xenografts. The oncolytic efficacy of MV-NIS was determined by measurement of tumor growth and mouse survival. RESULTS. Infection of human pancreatic cancer cell lines with MV-NIS in vitro resulted in syncytia formation, marked iodide uptake, and ultimately cell death. Tumor xenografts infected with MV-NIS concentrated radioiodine, allowing serial quantitative imaging with 123I micro-SPECT/CT. IT MV-NIS therapy of human pancreatic cancer xenografts resulted in a significant reduction in tumor volume and increased survival time of the treated mice compared with the control mice. CONCLUSION. MV-NIS efficiently infects human pancreatic tumor cells and results in sufficient radioiodine uptake to enable noninvasive serial imaging and quantitation of the intensity, distribution, and time course of NIS gene expression. MV-NIS also shows oncolytic activity in human pancreatic cancer xenografts: Tumor growth is reduced and survival is increased in mice treated with the virus.

AB - OBJECTIVE. Our objectives were to, first, determine the oncolytic potential of an engineered measles virus expressing the sodium-iodide symporter gene (MV-NIS) for intratumoral (IT) therapy of pancreatic cancer and, second, evaluate NIS as a reporter gene for in vivo monitoring and quantitation of MV-NIS delivery, viral spread, and gene expression in this tumor model. MATERIALS AND METHODS. Cultured human pancreatic cancer cells were infected with MV-NIS. Light microscopy, cell viability, and iodide uptake assays were used to confirm viral infection and NIS gene expression and function in vitro. Human pancreatic tumor xenografts were established in mice and infected via IT MV-NIS injections. NIS-mediated IT iodide uptake was quantitated by 123I micro-SPECT/CT. IT MV-NIS infection was confirmed by immunohistochemistry of excised pancreatic xenografts. The oncolytic efficacy of MV-NIS was determined by measurement of tumor growth and mouse survival. RESULTS. Infection of human pancreatic cancer cell lines with MV-NIS in vitro resulted in syncytia formation, marked iodide uptake, and ultimately cell death. Tumor xenografts infected with MV-NIS concentrated radioiodine, allowing serial quantitative imaging with 123I micro-SPECT/CT. IT MV-NIS therapy of human pancreatic cancer xenografts resulted in a significant reduction in tumor volume and increased survival time of the treated mice compared with the control mice. CONCLUSION. MV-NIS efficiently infects human pancreatic tumor cells and results in sufficient radioiodine uptake to enable noninvasive serial imaging and quantitation of the intensity, distribution, and time course of NIS gene expression. MV-NIS also shows oncolytic activity in human pancreatic cancer xenografts: Tumor growth is reduced and survival is increased in mice treated with the virus.

KW - Gene therapy

KW - Measles virus

KW - Micro-SPECT/CT

KW - Molecular imaging

KW - Pancreatic cancer

KW - Sodium-iodide symporter

KW - Viral therapy

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