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


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 i.t. MV-NIS injections. NIS-mediated i.t. iodide uptake was quantitated by (123)I micro-SPECT/CT. i.t. 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 (123)I micro-SPECT/CT. i.t. 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.


CONCLUSIONS
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.
Carlson
Stephanie K
SK
Department of Radiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. scarlson@mayo.edu
Classic
Kelly L
KL
Hadac
Elizabeth M
EM
Dingli
David
D
Bender
Claire E
CE
Kemp
Bradley J
BJ
Russell
Stephen J
SJ
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D015336:Molecular Probe Techniques; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy* / Q000821:virology; D015202:Protein Engineering / Q000379:methods; D011877:Radionuclide Imaging; D027981:Symporters / Q000378:metabolism* / Q000627:therapeutic use*; D014162:Transfection / Q000379:methods; D000099209:Sodium-Iodide Symporters
D027981:Symporters; D000099209:Sodium-Iodide Symporters