Skip to main content
SpringerLink
Log in

Real-Time Fluorescence Imaging of Abdominal, Pleural, and Lymphatic Metastases

  • Protocol
  • First Online:
In Vivo Cellular Imaging Using Fluorescent Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 872))

Abstract

Virally-directed fluorescence imaging has the potential to revolutionize intra-operative oncologic staging and tumor resection. Many viruses genetically engineered to specifically infect tumor cells as cancer therapy can be further modified to have a visible marker gene for cancer staging. In this chapter, we describe such a herpes simplex virus (HSV) modified to be detected by fluorescence. Other viruses so designed can be similarly used in cancer detection and staging. Replication-competent, tumor-specific HSV NV1066 expresses green fluorescent protein (GFP) in infected cancer cells. One single dose of NV1066 administered via intratumor, intracavitary, or systemic injection can spread within and across body cavities to target tumor cells while sparing normal tissue cells from infection. Tumors otherwise invisible by conventional laparoscopy appear green with the use of an endoscope equipped with a fluorescent filter. Furthermore, with GFP expression easily visualized by stereomicroscopy, microscopic, and pathologic analysis is significantly enhanced. This chapter addresses NV1066-directed visualization of peritoneal, pleural, and lymphatic metastases. This chapter also provides protocols for the production of tumor models in various body cavities in rodents.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Jarnagin, W.R., Conlon, K., Bodniewicz, J., Dougherty, E., DeMatteo, R.P., Blumgart, L.H., et al. (2001) A clinical scoring system predicts the yield of diagnostic laparoscopy in patients with potentially resectable hepatic colorectal metastases. Cancer 91(6), 1121–1128.

    Article  PubMed  CAS  Google Scholar 

  2. Paraskeva, P.A., Purkayastha, S., Darzi, A. (2004) Laparoscopy for malignancy: current status. Seminars in Laparoscopic Surgery 11(1), 27–36.

    PubMed  CAS  Google Scholar 

  3. Parra, J.L., Reddy, K.R. (2004) Diagnostic laparoscopy. Endoscopy 36(4), 289–293.

    Article  PubMed  CAS  Google Scholar 

  4. Corvera, C.U., Blumgart, L.H., Darvishian, F., Klimstra, D.S., DeMatteo, R., Fong, Y., et al. (2005) Clinical and pathologic features of proximal biliary strictures masquerading as hilar cholangiocarcinoma. J Am Coll Surg 201(6), 862–869.

    Article  PubMed  Google Scholar 

  5. Sugarbaker, P.H. (2004) Managing the peritoneal surface component of gastrointestinal cancer. Part 2. Perioperative intraperitoneal chemotherapy. Oncology (Williston Park) 18(2), 207–219.

    Google Scholar 

  6. Sugarbaker, P.H. (2001) Cytoreductive surgery and peri-operative intraperitoneal chemotherapy as a curative approach to pseudomyxoma peritonei syndrome. European Journal Of Surgical Oncology 27(3), 239–243.

    Article  PubMed  CAS  Google Scholar 

  7. Yonemura, Y., Bandou, E., Kinoshita, K., Kawamura, T., Takahashi, S., Endou, Y., et al. (2003) Effective therapy for peritoneal dissemination in gastric cancer. Surgical Oncology Clinics of North America 12(3), 635–648.

    Article  PubMed  Google Scholar 

  8. Rusch, V.W., Rosenzweig, K., Venkatraman, E., Leon, L., Raben, A., Harrison, L., et al. (2001) A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 122(4), 788–795.

    Article  PubMed  CAS  Google Scholar 

  9. Jaklitsch, M.T., Grondin, S.C., Sugarbaker, D.J. (2001) Treatment of malignant mesothelioma. World J Surg 25(2), 210–217.

    Article  PubMed  CAS  Google Scholar 

  10. Rusch, V.W. (1999) Indications for pneumonectomy. Extrapleural pneumonectomy. Chest Surg Clin N Am 9(2), 327–338.

    CAS  Google Scholar 

  11. Rusch, V.W., Venkatraman, E.S. (1999) Important prognostic factors in patients with malignant pleural mesothelioma, managed surgically. Ann Thorac Surg 68(5), 1799–1804.

    Article  PubMed  CAS  Google Scholar 

  12. Sugarbaker, P.H. Managing the peritoneal surface component of gastrointestinal cancer. Part 1. Patterns of dissemination and treatment options. Oncology (Williston Park) 18(1), 51–59.

    Google Scholar 

  13. Verwaal, V.J., van Ruth,. S, Witkamp, A., Boot, H., van Slooten, G., Zoetmulder, F.A. (2005) Long-term survival of peritoneal carcinomatosis of colorectal origin. Annals of Surgical Oncology 12(1), 65–71.

    Article  PubMed  Google Scholar 

  14. D’Angelica, M., Fong, Y., Weber, S., Gonen, M., DeMatteo, R.P., Conlon, K., et al. (2003) The role of staging laparoscopy in hepatobiliary malignancy: prospective analysis of 401 cases. Annals of Surgical Oncology 10(2), 183–189.

    Article  PubMed  Google Scholar 

  15. Jiao, X., Krasna, M.J. (2002) Clinical significance of micrometastasis in lung and esophageal cancer: a new paradigm in thoracic oncology. Ann Thorac Surg 74(1), 278–284.

    Article  PubMed  Google Scholar 

  16. Veronesi, U., Galimberti, V., Mariani, L., Gatti, G., Paganelli, G., Viale, G., et al. (2005) Sentinel node biopsy in breast cancer: early results in 953 patients with negative sentinel node biopsy and no axillary dissection. European Journal Of Cancer 41(2), 231–237.

    Article  PubMed  Google Scholar 

  17. Kelley, M.C., Hansen, N., McMasters, K.M. (2004) Lymphatic mapping and sentinel lymphadenectomy for breast cancer. American Journal Of Surgery 188(1), 49–61.

    Article  PubMed  Google Scholar 

  18. Liu, T.C., Galanis, E., Kirn, D. (2007) Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress. Nat Clin Pract Oncol 4(2), 101–117.

    Article  PubMed  CAS  Google Scholar 

  19. Reinblatt, M., Pin, R.H., Fong, Y. (2007) Herpes viral oncolysis: a novel cancer therapy. J Am Coll Surg 205(4 Suppl), S69–S75.

    Article  PubMed  Google Scholar 

  20. Bennett, J.J., Delman, K.A., Burt, B.M., Mariotti, A., Malhotra, S., Zager, J., et al. (2002) Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer. Cancer Gene Therapy 9(11), 935–945.

    Article  PubMed  CAS  Google Scholar 

  21. Wong, R.J., Joe, J.K., Kim, S.H., Shah, J.P., Horsburgh, B., Fong, Y.M. (2002) Oncolytic herpesvirus effectively treats murine squamous cell carcinoma and spreads by natural lymphatics to treat sites of lymphatic Metastases. Human Gene Therapy 13(10), 1213–1223.

    Article  PubMed  CAS  Google Scholar 

  22. Wong, R.J., Kim, S.H., Joe, J.K., Shah, J.P., Johnson, P.A., Fong, Y. (2001) Effective treatment of head and neck squamous cell carcinoma by an oncolytic herpes simplex virus. Journal of the American College of Surgeons 193(1), 12–21.

    Article  PubMed  CAS  Google Scholar 

  23. McAuliffe, P.F., Jarnagin, W.R., Johnson, P., Delman, K.A., Federoff, H., Fong, Y. (2000) Effective treatment of pancreatic tumors with two multimutated herpes simplex oncolytic viruses. Journal of Gastrointestinal Surgery 4(6), 580–588.

    Article  PubMed  CAS  Google Scholar 

  24. Stiles, B.M., Bhargava, A., Adusumilli, P.S., Stanziale, S.F., Kim, T.H., Rusch,V.W., et al. (2003) The replication-competent oncolytic herpes simplex mutant virus NV1066 is effective in the treatment of esophageal cancer. Surgery 134(2), 357–364.

    Article  PubMed  Google Scholar 

  25. Stanziale, S.F., Petrowsky, H., Adusumilli, P.S., Ben Porat, L., Gonen, M., Fong, Y. (2004) Infection with oncolytic herpes simplex virus-1 induces apoptosis in neighboring human cancer cells: a potential target to increase anticancer activity. Clinical Cancer Research 10(9), 3225–3232.

    Article  PubMed  CAS  Google Scholar 

  26. Adusumilli, P.S., Eisenberg, D.P., Stiles, B.M., Hendershott, K.J., Stanziale, S.F., Chan, M.K., et al. (2006) Virally-directed fluorescent imaging (VFI) can facilitate endoscopic staging. Surgical Endoscopy 20(4), 628–635.

    Article  PubMed  CAS  Google Scholar 

  27. Stanziale, S.F., Stiles, B.M., Bhargava, A., Kerns, S.A., Kalakonda, N., Fong, Y. (2004) Oncolytic herpes simplex virus-1 mutant expressing green fluorescent protein can detect and treat peritoneal cancer. Hum Gene Ther 15(6), 609–618.

    Article  PubMed  CAS  Google Scholar 

  28. Adusumilli, P.S., Eisenberg, D.P., Chun, Y.S., Ryu, K.W., Ben-Porat, L., Hendershott, K.J., et al. (2005) Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery. Journal of Gastrointestinal Surgery 9(8), 1138–1147.

    Article  PubMed  Google Scholar 

  29. Adusumilli, P.S., Stiles, B.M., Chan, M.K., Eisenberg, D.P., Yu, Z., Stanziale, S.F., et al. (2006) Real-time Diagnostic Imaging of Tumors and Metastases by Use of a Replication-competent Herpes Vector to Facilitate Minimally-Invasive Oncological Surgery. FASEB J 20(6), 726–728.

    PubMed  CAS  Google Scholar 

  30. Gahlen, J., Stern, J., Laubach, H.H., Pietschmann, M., Herfarth, C. (1999) Improving diagnostic staging laparoscopy using intraperitoneal lavage of delta-aminolevulinic acid (ALA) for laparoscopic fluorescence diagnosis. Surgery 126(3), 469–473.

    Article  PubMed  CAS  Google Scholar 

  31. Chalfie, M., Tu, Y., Euskirchen, G., Ward, W.W., Prasher, D.C. (1994) Green fluorescent protein as a marker for gene expression. Science 263(5148), 802–805.

    Article  PubMed  CAS  Google Scholar 

  32. Cormack, B.P., Valdivia, R.H., Falkow, S. (1996) FACS-optimized mutants of the green fluorescent protein (GFP). Gene 173(1 Spec No), 33–38.

    Google Scholar 

  33. Adusumilli, P.S., Eisenberg, D.P., Stiles, B.M., Chung, S., Chan, M.K., Rusch, V.W., et al. (2006) Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus. J Thorac Cardiovasc Surg 132(5), 1179–1188.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Susanne Carpenter & Yuman Fong

Authors
  1. Susanne Carpenter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuman Fong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuman Fong .

Editor information

Editors and Affiliations

  1. AntiCancer, Inc., Ostrow Street 7917, San Diego, 92111, California, USA

    Robert M. Hoffman

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media New York

About this protocol

Cite this protocol

Carpenter, S., Fong, Y. (2012). Real-Time Fluorescence Imaging of Abdominal, Pleural, and Lymphatic Metastases. In: Hoffman, R. (eds) In Vivo Cellular Imaging Using Fluorescent Proteins. Methods in Molecular Biology, vol 872. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-797-2_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-797-2_10

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-796-5

  • Online ISBN: 978-1-61779-797-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation