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Virally-directed fluorescent imaging (VFI) can facilitate endoscopic staging

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Surgical Endoscopy And Other Interventional Techniques Aims and scope Submit manuscript

Abstract

Background

Replication-competent, tumor specific herpes simplex virus NV1066 expresses green fluorescent protein (GFP) in infected cancer cells. We sought to determine the feasibility of GFP-guided imaging technology in the intraoperative detection of small tumor nodules.

Methods

Human cancer cell lines were infected with NV1066 at multiplicities of infection of 0.01, 0.1 and 1. Cancer cell specific infectivity, vector spread and GFP signal intensity were measured by flow cytometry and time-lapse digital imaging (in vitro); and by use of a stereomicroscope and endoscope equipped with a fluorescent filter (in vivo).

Results

NV1066 infected all cancer cell lines and expressed GFP at all MOIs. GFP signal was significantly higher than the autofluorescence of normal cells. One single dose of NV1066 spread within and across body cavities and selectively infected tumor nodules sparing normal tissue. Tumor nodules undetectable by conventional thoracoscopy and laparoscopy were identified by GFP fluorescence.

Conclusion

Virally-directed fluorescent imaging (VFI) is a real-time novel molecular imaging technology that has the potential to enhance the intraoperative detection of endoluminal or endocavitary tumor nodules.

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Acknowledgments

The authors thank Liza Marsh and Scott Tuorto of the Department of Surgery at Memorial Sloan-Kettering Cancer Center for their editorial assistance. We also thank Brian Horsburgh, Ph.D. and Medigene, Inc. for constructing and providing us with the NV1066 virus. Special thanks to Kan Matsumoto from Olympus America Inc., for design and construction of the fluorescent endoscopic system. Supported in part by AACR-AstraZeneca Cancer Research and Prevention fellowship (P.S.A), grants RO1 CA 75416 and RO1 CA/DK80982 (Y.F.) from the National Institutes of Health, grant MBC-99366 (Y.F.) from the American Cancer Society, grant BC024118 from the US Army (Y.F.), grant IMG0402501 from the Susan G. Komen Foundation (Y.F. and P.S.A) and grant 032047 from Flight Attendant Medical Research Institute (Y.F. and P.S.A.)

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Authors and Affiliations

  1. Department of Surgery, Memorial Sloan–Kettering Cancer Center, New York, NY, 10021, USA

    P. S. Adusumilli, D. P. Eisenberg, B. M. Stiles, K. J. Hendershott, S. F. Stanziale, M.-K. Chan, M. Hezel, V. W. Rusch & Y. Fong

  2. Molecular Cytology Core Facility, Memorial Sloan–Kettering Cancer Center, New York, NY, 10021, USA

    R. Huq

Authors
  1. P. S. Adusumilli
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  2. D. P. Eisenberg
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  3. B. M. Stiles
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  4. K. J. Hendershott
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  5. S. F. Stanziale
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  6. M.-K. Chan
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  7. M. Hezel
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  8. R. Huq
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  9. V. W. Rusch
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  10. Y. Fong
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Corresponding author

Correspondence to Y. Fong.

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R. Huq: Molecular Cytology Core Facility

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Adusumilli, P.S., Eisenberg, D.P., Stiles, B.M. et al. Virally-directed fluorescent imaging (VFI) can facilitate endoscopic staging. Surg Endosc 20, 628–635 (2006). https://doi.org/10.1007/s00464-005-0259-6

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  • DOI: https://doi.org/10.1007/s00464-005-0259-6

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