Utility of a herpes oncolytic virus for the detection of neural invasion by cancer.
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 [(18)F]-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.
Gil
Ziv
Z
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Kelly
Kaitlyn J
KJ
Brader
Peter
P
Shah
Jatin P
JP
Fong
Yuman
Y
Wong
Richard J
RJ
D000230:Adenocarcinoma / Q000378:metabolism / Q000821:virology*; D000818:Animals; D018450:Disease Progression; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D050504:Oncolytic Viruses / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000821:virology*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000821:virology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000502:physiology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011505:Protein-Tyrosine Kinases