HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Carlson, S. K. Articles by Russell, S. J. Search for Related Content PubMed PubMed Citation Articles by Carlson, S. K. Articles by Russell, S. J. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?

Quantitative Molecular Imaging of Viral Therapy for Pancreatic Cancer Using an Engineered Measles Virus Expressing the Sodium-Iodide Symporter Reporter Gene

¹ Department of Radiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905.
² Division of Molecular Medicine, Mayo Clinic, Rochester, MN.
³ Section of Safety and Security, Mayo Clinic, Rochester, MN.
⁴ Division of Hematology, Mayo Clinic, Rochester, MN.

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.

Keywords: gene therapy • measles virus • micro-SPECT/CT • molecular imaging • pancreatic cancer • sodium-iodide symporter • viral therapy

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?