title: The use of the NIS reporter gene for optimizing oncolytic virotherapy.
abstract: BACKGROUND
  Oncolytic viruses are experimental cancer therapies being translated to the clinic. They are unique in their ability to amplify within the body, therefore requiring careful monitoring of viral replication and biodistribution. Traditional monitoring strategies fail to recapitulate the dynamic nature of oncolytic virotherapy. Consequently, clinically relevant, noninvasive, high resolution strategies are needed to effectively track virotherapy in real time.
  
  
  METHODS
  The expression of the sodium iodide symporter (NIS) reporter gene is tightly coupled to viral genome replication and mediates radioisotope concentration, allowing noninvasive molecular nuclear imaging of active viral infection with high resolution. This provides insight into replication kinetics, biodistribution, the impact of vector design, administration, and dosing on therapeutic outcomes, and highlights the heterogeneity of spatial distribution and temporal evolution of infection. NIS-mediated imaging in clinical trials confirms the feasibility of this technology to noninvasively and longitudinally observe oncolytic virus infection, replication, and distribution.
  
  
  CONCLUSIONS
  NIS-mediated imaging provides detailed functional and molecular information on the evolution of oncolytic virus infection in living animals. The use of NIS reporter gene imaging has rapidly advanced to provide unparalleled insight into the spatial and temporal context of oncolytic infection which will be integral to optimization of oncolytic treatment strategies.
authors.affiliation: a Mayo Clinic, Department of Molecular Medicine , Rochester , MN 55905 , USA.|b Mayo Graduate School, Center for Clinical and Translational Science , Rochester , MN 55905 , USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Miller
authors.affiliation: a Mayo Clinic, Department of Molecular Medicine , Rochester , MN 55905 , USA.|c Mayo Clinic, Division of Hematology , Rochester , MN 55905 , USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000009:adverse effects / Q000235:genetics; D003952:Diagnostic Imaging; D017930:Genes, Reporter; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods* / Q000592:standards; D050504:Oncolytic Viruses / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D027981:Symporters / Q000235:genetics* / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014779:Virus Replication / Q000235:genetics; D000099209:Sodium-Iodide Symporters
chemical_list: D019496:Cancer Vaccines; D027981:Symporters; D000099209:Sodium-Iodide Symporters
keywords: NIS; molecular imaging; oncolytic virus; reporter gene