Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery Journal Article


Authors: Adusumilli, P. S.; Eisenberg, D. P.; Chun, Y. S; Ryu, K. W.; Ben-Porat, L.; Hendershott, K. J.; Chan, M. K.; Huq, R.; Riedl, C. C.; Fong, Y.
Article 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. © 2005 The Society for Surgery of the Alimentary Tract.
Keywords: genetics; flow cytometry; methodology; mouse; animal; metabolism; animals; mice; peritoneal neoplasms; green fluorescent protein; tumor cells, cultured; physiology; cell culture; minimal residual disease; neoplasm, residual; gene therapy; oncolytic virus; oncolytic viruses; green fluorescent proteins; fluorescence microscopy; microscopy, fluorescence; herpesvirus 1, human; virus replication; herpes simplex virus 1; herpes simplex virus; peritoneum tumor; cytopathogenic effect; cytopathogenic effect, viral; peritoneal carcinomatosis; peritonectomy; oncolytic viral therapy
Journal Title: Journal of Gastrointestinal Surgery
Volume: 9
Issue: 8
ISSN: 1091-255X
Publisher: Springer  
Date Published: 2005-11-01
Start Page: 1138
End Page: 1147
Language: English
DOI: 10.1016/j.gassur.2005.06.029
PUBMED: 16269385
PROVIDER: scopus
PMCID: PMC1783680
DOI/URL:
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 24 October 2012" - "Source: Scopus"
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MSK Authors
  1. Christopher Riedl
    60 Riedl
  2. Keun Won Ryu
    1 Ryu
  3. Yun Shin Chun
    8 Chun
  4. Yuman Fong
    775 Fong
  5. Mei-Ki Chan
    25 Chan
  6. Rumana Huq
    6 Huq