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

<h4>Introduction</h4>Oncolytic 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-...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e6f8ae9579b4c7fa00b11b9b873054d
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spelling	oai:doaj.org-article:0e6f8ae9579b4c7fa00b11b9b873054d2021-11-18T07:08:30ZImaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.1932-620310.1371/journal.pone.0041647https://doaj.org/article/0e6f8ae9579b4c7fa00b11b9b873054d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22912675/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Oncolytic 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.<h4>Methods</h4>GLV-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.<h4>Results</h4>GLV-1h153 successfully facilitated time-dependent intracellular uptake of (131)I in PANC-1 cells with a maximum uptake at 24 hours postinfection (P<0.05). In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 10(9) plaque-forming unit (PFU)/gm tissue, with the virus mainly cleared from all other major organs. Tumor infection by GLV-1h153 was confirmed via optical imaging and histology. GLV-1h153 facilitated imaging virus replication in tumors via PET even at 8 hours post radiotracer injection, with a mean %ID/gm of 3.82 ± 0.46 (P<0.05) 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV-1h153-infected tumors were detected via (124)I-PET and 99m-technecium-scintigraphy.<h4>Conclusion</h4>GLV-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.Dana HaddadChun-Hao ChenSean CarlinGerd SilberhumerNanhai G ChenQian ZhangValerie LongoSusanne G CarpenterArjun MittraJoshua CarsonJoyce AuMithat GonenPat B ZanzonicoAladar A SzalayYuman FongPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e41647 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.
description	<h4>Introduction</h4>Oncolytic 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.<h4>Methods</h4>GLV-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.<h4>Results</h4>GLV-1h153 successfully facilitated time-dependent intracellular uptake of (131)I in PANC-1 cells with a maximum uptake at 24 hours postinfection (P<0.05). In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 10(9) plaque-forming unit (PFU)/gm tissue, with the virus mainly cleared from all other major organs. Tumor infection by GLV-1h153 was confirmed via optical imaging and histology. GLV-1h153 facilitated imaging virus replication in tumors via PET even at 8 hours post radiotracer injection, with a mean %ID/gm of 3.82 ± 0.46 (P<0.05) 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV-1h153-infected tumors were detected via (124)I-PET and 99m-technecium-scintigraphy.<h4>Conclusion</h4>GLV-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.
format	article
author	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
author_facet	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
author_sort	Dana Haddad
title	Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.
title_short	Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.
title_full	Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.
title_fullStr	Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.
title_full_unstemmed	Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.
title_sort	imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0e6f8ae9579b4c7fa00b11b9b873054d
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Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter.

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