title: An oncolytic vaccinia virus expressing the human sodium iodine symporter prolongs survival and facilitates SPECT/CT imaging in an orthotopic model of malignant pleural mesothelioma.
abstract: BACKGROUND
  The purpose of this work was to examine the ability of an oncolytic vaccinia virus expressing the human sodium iodine transporter (hNIS) to provide real time monitoring of viral therapy and effective treatment of malignant pleural mesothelioma (MPM).
  
  
  METHODS
  Infectivity and cytotoxic effects of GLV-1h153 on mesothelioma cell lines of all histologic subtypes were assayed in vitro. Viral replication was examined by standard viral plaque assay. Orthotopic MPM xenografts were generated in athymic nude mice, treated with intrapleural GLV-1h153, and assessed for effect on tumor burden and survival. Orthotopic tumors were also imaged on single photon emission computed tomography (SPECT)/computed tomography (CT) after (131)I administration.
  
  
  RESULTS
  GLV-1h153-infected and killed all cell lines in a time- and concentration-dependent manner. Viral replication demonstrated a >2.5-log increase in titer over 4 days. Intrapleural treatment of orthotopic MPM xenografts resulted in a significant decrease in tumor burden 1 week after treatment and an improvement in survival. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by (131)I-SPECT/CT via expression of hNIS in infected tissue.
  
  
  CONCLUSIONS
  Our results suggest that GLV-1h153 may be a promising therapeutic agent for MPM and warrants further investigation.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Belin
authors.forename: Justin W
authors.initials: JW
authors.lastname: Ady
authors.forename: Christina
authors.initials: C
authors.lastname: Lewis
authors.forename: Drew
authors.initials: D
authors.lastname: Marano
authors.forename: Sepideh
authors.initials: S
authors.lastname: Gholami
authors.forename: Kelly
authors.initials: K
authors.lastname: Mojica
authors.forename: Clarisse
authors.initials: C
authors.lastname: Eveno
authors.forename: Valerie
authors.initials: V
authors.lastname: Longo
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008654:Mesothelioma / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D051379:Mice; D064847:Multimodal Imaging / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics*; D010997:Pleural Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D049268:Positron-Emission Tomography; D027981:Symporters / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D014616:Vaccinia virus / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
chemical_list: D027981:Symporters; D000099209:Sodium-Iodide Symporters
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