title: Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery.
abstract: Completeness of cytoreduction is an independent prognostic factor after cure-intended surgery for peritoneal carcinomatosis. NV1066, a genetically engineered herpes simplex virus carrying the transgene for green fluorescent protein, selectively infects cancer cells. We sought to determine the feasibility of virally directed fluorescent imaging in the intraoperative detection of minimal residual disease after cytoreductive surgery. NV1066 infected human gastric cancer cells, OCUM-2MD3, and mesothelioma JMN cells at all doses. The infected cells expressed green fluorescent protein and were killed. OCUM-2MD3, and mesothelioma JMN cells at all doses. Peritoneal carcinomatosis was established in mice by injection of OCUM cells into the peritoneal cavity. Forty-eight hours after intraperitoneal injection of NV1066, two experienced surgeons resected all visible disease and identified mice free of disease. Eight of 13 mice thought to be free of disease were found to have residual disease as identified by green fluorescence (mean number of observations: 5; range: 1-9). Residual disease was most frequently observed in the retroperitoneum, pelvis, peritoneal surface, and liver. Specificity of NV1066 infection to tumor nodules was confirmed by immunohistochemistry and by polymerase chain reaction for viral gene. Virally directed fluorescent imaging, a novel molecular imaging technology, can be used for real-time visualization of minimal residual disease after cytoreductive surgery and can improve the completeness of cure-intended resection.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
authors.forename: David P
authors.initials: DP
authors.lastname: Eisenberg
authors.forename: Yun Shin
authors.initials: YS
authors.lastname: Chun
authors.forename: Keun-Won
authors.initials: KW
authors.lastname: Ryu
authors.forename: Leah
authors.initials: L
authors.lastname: Ben-Porat
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Hendershott
authors.forename: Mei-Ki
authors.initials: MK
authors.lastname: Chan
authors.forename: Rumana
authors.initials: R
authors.lastname: Huq
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Riedl
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D003588:Cytopathogenic Effect, Viral; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D018365:Neoplasm, Residual / Q000175:diagnosis*; D050504:Oncolytic Viruses; D010534:Peritoneal Neoplasms / Q000175:diagnosis* / Q000601:surgery; D014407:Tumor Cells, Cultured; D014779:Virus Replication
chemical_list: D049452:Green Fluorescent Proteins