Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.

Autor: Dana Haddad, Chun-Hao Chen, Sean Carlin, Gerd Silberhumer, Nanhai G Chen, Qian Zhang, Valerie Longo, Susanne G Carpenter, Arjun Mittra, Joshua Carson, Joyce Au, Mithat Gonen, Pat B Zanzonico, Aladar A Szalay, Yuman Fong
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS ONE, Vol 7, Iss 8, p e41647 (2012)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0041647
Popis: IntroductionOncolytic viruses show promise for treating cancer. However, to assess therapy and potential toxicity, a noninvasive imaging modality is needed. This study aims to determine the in vivo biodistribution, and imaging and timing characteristics of a vaccinia virus, GLV-1h153, encoding the human sodium iodide symporter (hNIS.MethodsGLV-1h153 was modified from GLV-1h68 to encode the hNIS gene. Timing of cellular uptake of radioiodide (131)I in human pancreatic carcinoma cells PANC-1 was assessed using radiouptake assays. Viral biodistribution was determined in nude mice bearing PANC-1 xenografts, and infection in tumors confirmed histologically and optically via Green Fluorescent Protein (GFP) and bioluminescence. Timing characteristics of enhanced radiouptake in xenografts were assessed via (124)I-positron emission tomography (PET). Detection of systemic administration of virus was investigated with both (124)I-PET and 99m-technecium gamma-scintigraphy.ResultsGLV-1h153 successfully facilitated time-dependent intracellular uptake of (131)I in PANC-1 cells with a maximum uptake at 24 hours postinfection (PConclusionGLV-1h153 is a promising oncolytic agent against pancreatic cancer with a promising biosafety profile. GLV-1h153 facilitated time-dependent hNIS-specific radiouptake in pancreatic cancer cells, facilitating detection by PET with both intratumoral and systemic administration. Therefore, GLV-1h153 is a promising candidate for the noninvasive imaging of virotherapy and warrants further study into longterm monitoring of virotherapy and potential radiocombination therapies with this treatment and imaging modality.
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