title: A vaccinia virus encoding the human sodium iodide symporter facilitates long-term image monitoring of virotherapy and targeted radiotherapy of pancreatic cancer.
abstract: To assess therapeutic response and potential toxicity of oncolytic virotherapy, a noninvasive, deep-tissue imaging modality is needed. This study aimed to assess the feasibility, parameters, and determining factors of serial imaging and long-term monitoring of virotherapy and the therapeutic response of pancreatic cancer xenografts treated with a vaccinia virus carrying the human sodium iodide symporter GLV-1h153.
  
  
  METHODS
  Pancreatic cancer xenografts (PANC-1) in nude mice were treated systemically or intratumorally with GLV-1h153 and serially imaged using (124)I PET at 1, 2, 3, and 5 wk after viral injection. Signal intensity was compared with tumor therapeutic response and optical imaging, and tumors were histologically analyzed for morphology and the presence of virus. Autoradiography was performed using technetium-pertechnetate and γ-scintigraphy to assess determining factors for radiouptake in tumors. Finally, the enhanced therapeutic effect of combination therapy with GLV-1h153 and systemic radioiodine was assessed.
  
  
  RESULTS
  GLV-1h153 successfully facilitated serial long-term imaging of virotherapy, with PET signal intensity correlating to tumor response. GLV-1h153 colonization of tumors mediated radioiodine uptake at potentially therapeutic doses. Successful radiouptake required the presence of virus, adequate blood flow, and viable tissue, whereas loss of signal intensity was linked to tumor death and necrosis. Finally, combining systemically administered GLV-1h153 and (131)I led to enhanced tumor kill when compared with virus or (131)I alone (P < 0.01).
  
  
  CONCLUSIONS
  GLV-1h153 is a promising oncolytic agent for the treatment, long-term imaging, and monitoring of therapeutic response in a xenograft model of pancreatic cancer. GLV-1h153 provided insight into tumor biologic activity and facilitated enhanced tumor kill when combined with systemic targeted radiotherapy. These results warrant further investigation into parameters and potential synergistic effects of combination therapy.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Haddad
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: Sean
authors.initials: S
authors.lastname: Carlin
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Nanhai G
authors.initials: NG
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yong A
authors.initials: YA
authors.lastname: Yu
authors.forename: Valerie
authors.initials: V
authors.lastname: Longo
authors.forename: Kelly
authors.initials: K
authors.lastname: Mojica
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Aguilar
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; D005240:Feasibility Studies; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D050130:Oncolytic Virotherapy / Q000379:methods*; D061848:Optical Imaging; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D049268:Positron-Emission Tomography; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D027981:Symporters / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D014616:Vaccinia virus / Q000235:genetics*; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters