Utility of a herpes oncolytic virus for the detection of neural invasion by cancer Journal Article


Authors: Gil, Z.; Kelly, K. J.; Brader, P.; Shah, J. P.; Fong, Y.; Wong, R. J.
Article Title: Utility of a herpes oncolytic virus for the detection of neural invasion by cancer
Abstract: Prostate, pancreatic, and head and neck carcinomas have a high propensity to invade nerves. Surgical resection is a treatment modality for these patients, but it may incur significant deficits. The development of an imaging method able to detect neural invasion (NI) by cancer cells may guide surgical resection and facilitate preservation of normal nerves. We describe an imaging method for the detection of NI using a herpes simplex virus, NV1066, carrying tyrosine kinase and enhanced green fluorescent protein (eGFP). Infection of pancreatic (MiaPaCa2), prostate (PC3 and DU145), and adenoid cystic carcinoma (ACC3) cell lines with NV1066 induced a high expression of eGFP in vitro. An in vivo murine model of NI was established by implanting tumors into the sciatic nerves of nude mice. Nerves were then injected with NV1066, and infection was confirmed by polymerase chain reaction. Positron emission tomography with [ 18F]-2′-fluoro-2′-deoxyarabinofuranosyl-5-ethyluracil performed showed significantly higher uptake in NI than in control animals. Intraoperative fluorescent stereoscopic imaging revealed eGFP signal in NI treated with NV1066. These findings show that NV1066 may be an imaging method to enhance the detection of nerves infiltrated by cancer cells. This method may improve the diagnosis and treatment of patients with neurotrophic cancers by reducing injury to normal nerves and facilitating identification of infiltrated nerves requiring resection. Copyright © 2008 Neoplasia Press, Inc. All rights reserved.
Keywords: controlled study; protein expression; human cell; nonhuman; pancreatic neoplasms; positron emission tomography; polymerase chain reaction; adenocarcinoma; mouse; animals; mice; animal tissue; infection; animal experiment; animal model; in vivo study; neurons; in vitro study; tumor cells, cultured; protein tyrosine kinase; mice, inbred balb c; cancer invasion; prostatic neoplasms; nude mouse; reverse transcriptase polymerase chain reaction; rna, messenger; intraoperative period; disease progression; cancer cell; fluorodeoxyglucose f 18; positron-emission tomography; oncolytic virus; simplexvirus; oncolytic viruses; imaging; green fluorescent proteins; protein-tyrosine kinases; adenoid cystic carcinoma; herpes simplex virus; pancreas disease; prostate carcinoma; cancer transplantation; enhanced green fluorescent protein; sciatic nerve; stereoscopic vision; nerve cell inhibition
Journal Title: NeoPlasia
Volume: 10
Issue: 4
ISSN: 1522-8002
Publisher: Elsevier Science Inc.  
Date Published: 2008-04-01
Start Page: 347
End Page: 353
Language: English
DOI: 10.1593/neo.07981
PUBMED: 18392138
PROVIDER: scopus
PMCID: PMC2288543
DOI/URL:
Notes: --- - "Cited By (since 1996): 7" - "Export Date: 17 November 2011" - "CODEN: NEOPF" - "Source: Scopus"
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  1. Ziv A Gil
    17 Gil
  2. Peter Brader
    25 Brader
  3. Kaitlyn J Kelly
    31 Kelly
  4. Richard J Wong
    416 Wong
  5. Yuman Fong
    775 Fong
  6. Jatin P Shah
    722 Shah