Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery |
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Authors: | Prasad?S?Adusumilli David?P?Eisenberg Yun?Shin?Chun Keun-Won?Ryu Leah?Ben-?Porat Karen?J?Hendershott Mei-Ki?Chan Rumana?Huq Christopher?C?Riedl Email author" target="_blank">Yuman?FongEmail author |
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Institution: | (1) Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 10021 New York, NY;(2) Department of Surgery Statistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, New York;(3) Departments of Surgery Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, New York |
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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.
Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18,
2005 (oral presentation)
Supported in part by AstraZeneca Cancer Research and Prevention fellowship (P.S.A), training grant T 32 CA09501 (D.P.E and
K.J.H.), grants RO1 CA 76416 and RO1 CA/DK80982 (Y.F.) from the National Institutes of Health, grant BC024118 from the U.S.
Army (Y.F.), grant IMG0402501 from the Susan G. Komen Foundation (Y.F. and P.S.A), and grant 032047 from the Flight Attendant
Medical Research Institute (Y.F. and P.S.A). |
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Keywords: | Herpes simplex virus oncolytic viral therapy peritoneal carcinomatosis peritonectomy gene therapy |
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