title: Enhancing Expression of Functional Human Sodium Iodide Symporter and Somatostatin Receptor in Recombinant Oncolytic Vaccinia Virus for In Vivo Imaging of Tumors.
abstract: Oncolytic virus (OV) therapy has emerged as a novel tool in our therapeutic arsenals for fighting cancer. As a live biologic agent, OV has the ability to target and selectively amplify at the tumor sites. We have reported that a vaccinia-based OV (Pexa-Vec) has shown good efficacy in preclinical models and in clinical trials. To give an additional tool to clinicians to allow both treatment of the tumor and improved visualization of tumor margins, we developed new viral-based platforms with 2 specific gene reporters.
  
  
  
  We incorporated the human sodium iodide symporter (hNIS) and the human somatostatin receptor 2 (hSSR2) in the vaccinia-based OV and tested viral constructs for their abilities to track and treat tumor development in vivo.
  
  
  
  Early and high-level expression of hNIS is detrimental to the recombinant virus, leading to the aggregation of hNIS protein and early cell death. Putting hNIS under a late synthetic promoter allowed a higher functional expression of the protein and much stronger123I or99Tc uptake. In vivo, the hNIS-containing virus infected and amplified in the tumor site, showing a better efficacy than the parental virus. The hNIS expression at the tumor site allowed for the imaging of viral infection and tumor regression. Similarly, hSSR2-containing OV vaccinia infected and lysed cancer cells.
  
  
  
  When tumor-bearing mice were given hNIS- and hSSR2-containing OV,99Tc and111In signals coalesced at the tumor, highlighting the power of using these viruses for tumor diagnosis and treatment.
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Jiahu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Rozanne
authors.initials: R
authors.lastname: Arulanandam
authors.affiliation: Cardiac PET Research, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Wassenaar
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Theresa
authors.initials: T
authors.lastname: Falls
authors.affiliation: Cardiac PET Research, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: Petryk
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Judith
authors.initials: J
authors.lastname: Paget
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Garson
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Catia
authors.initials: C
authors.lastname: Cemeus
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; and.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Vanderhyden
authors.affiliation: Cardiac PET Research, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: R Glenn
authors.initials: RG
authors.lastname: Wells
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Bell
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada fleboeuf@ohri.ca.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Le Boeuf
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology; D049268:Positron-Emission Tomography / Q000379:methods; D017481:Receptors, Somatostatin / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D027981:Symporters / Q000235:genetics*; D000068936:Theranostic Nanomedicine / Q000379:methods; D016896:Treatment Outcome; D015854:Up-Regulation / Q000235:genetics; D014616:Vaccinia virus / Q000502:physiology*; D000099209:Sodium-Iodide Symporters
chemical_list: D017481:Receptors, Somatostatin; D027981:Symporters; D000099209:Sodium-Iodide Symporters
keywords: GI; SPECT/CT; animal imaging; cancer imaging; hNIS; hSSR2; oncology; oncolytic viruses