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Image-Guided Oncologic Surgery Using Invisible Light: Completed Pre-Clinical Development for Sentinel Lymph Node Mapping

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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Invisible near-infrared (NIR) fluorescent light permits high sensitivity, real-time image-guidance during oncologic surgery without changing the look of the surgical field. In this study, we complete pre-clinical development of the technology for sentinel lymph node (SLN) mapping using a large animal model of spontaneous melanoma.

Methods

Sinclair swine with spontaneous melanoma metastatic to regional lymph nodes were used because of their similarity to human melanoma. Organic lymphatic tracers tested included FDA-approved indocyanine green adsorbed non-covalently to human serum albumin (HSA), and NIR fluorophore CW800 conjugated covalently to HSA (HSA800). The inorganic/organic hybrid tracer tested was type II NIR quantum dots with an anionic coating. Primary tumors received four peri-tumoral injections of each tracer, with a fluorophore dose of 100 pmol to 1 nmol per injection. SLN mapping and image-guided resection were performed in real-time.

Results

Each of the 3 lymphatic tracers was injected into n = 4 separate primary melanomas in a total of 6 animals. All 12 injections resulted in identification of the SLN(s) and their associated lymphatic channels within 1 minute in 100% of cases, despite highly pigmented skin and black fur. Hydrodynamic diameter had a profound impact on tracer behavior in vivo.

Conclusions

This study completes the pre-clinical development of NIR fluorescence-guided SLN mapping and provides insight into imaging system optimization and tracer choice for future human clinical trials. The technology is likely to eliminate the need for radioactive and colored tracers, permits real-time image guidance throughout the procedure, and assists the pathologist in tissue analysis.

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References

  1. Lim YT, Kim S, Nakayama A, Stott NE, Bawendi MG, Frangioni JV. Selection of quantum dot wavelengths for biomedical assays and imaging. Mol Imaging 2003; 2:50–64

    Article  PubMed  CAS  Google Scholar 

  2. Frangioni JV. In vivo near-infrared fluorescence imaging. Curr Opin Chem Biol 2003; 7:626–34

    Article  PubMed  CAS  Google Scholar 

  3. Zaheer A, Lenkinski RE, Mahmood A, Jones AG, Cantley LC, Frangioni JV. In vivo near-infrared fluorescence imaging of osteoblastic activity. Nat Biotechnol 2001; 19:1148–54

    Article  PubMed  CAS  Google Scholar 

  4. Nakayama A, del Monte F, Hajjar RJ, Frangioni JV. Functional near-infrared fluorescence imaging for cardiac surgery and targeted gene therapy. Mol Imaging 2002; 1:365–77

    Article  PubMed  Google Scholar 

  5. De Grand AM, Frangioni JV. An operational near-infrared fluorescence imaging system prototype for large animal surgery. Technol Cancer Res Treat 2003; 2:553–62

    PubMed  Google Scholar 

  6. Kim S, Lim YT, Soltesz EG, et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 2004; 22:93–7

    Article  PubMed  CAS  Google Scholar 

  7. Gioux S, De Grand AM, Lee DS, Yazdanfarc S, Idoine JD, Lomnes SJ, Frangioni JV Improved optical sub-systems for intraoperative near-infrared fluorescence imaging. Proc of SPIE 2005; 6009:39–48

    Google Scholar 

  8. De Grand AM, Lomnes SJ, Lee DS, et al. Tissue-like phantoms for near-infrared fluorescence imaging system assessment and the training of surgeons. J Biomed Opt 2006; 11:14007

    Article  Google Scholar 

  9. Zaheer A, Wheat TE, Frangioni JV. IRDye78 conjugates for near-infrared fluorescence imaging. Mol Imaging 2002; 1:354–64

    Article  PubMed  CAS  Google Scholar 

  10. Ohnishi S, Lomnes SJ, Laurence RG, Gogbashian A, Mariani G, Frangioni JV. Organic alternatives to quantum dots for intraoperative near-infrared fluorescent sentinel lymph node mapping. Mol Imaging 2005; 4:172–81

    PubMed  Google Scholar 

  11. Mariani G, Moresco L, Viale G, et al. Radioguided sentinel lymph node biopsy in breast cancer surgery. J Nucl Med 2001; 42:1198–1215

    PubMed  CAS  Google Scholar 

  12. Schirrmeister H, Kotzerke J, Vogl F, et al. Prospective evaluation of factors influencing success rates of sentinel node biopsy in 814 breast cancer patients. Cancer Biother Radiopharm 2004; 19:784–90

    Article  PubMed  Google Scholar 

  13. Soltesz EG, Kim S, Laurence RG, et al. Intraoperative sentinel lymph node mapping of the lung using near-infrared fluorescent quantum dots. Ann Thorac Surg 2005; 79:269–77; discussion 269–77

    Article  PubMed  Google Scholar 

  14. Parungo CP, Ohnishi S, De Grand AM, et al. In vivo optical imaging of pleural space drainage to lymph nodes of prognostic significance. Ann Surg Oncol 2004; 11:1085–92

    Article  PubMed  Google Scholar 

  15. Parungo CP, Colson YL, Kim SW, Kim S, Cohn LH, Bawendi MG, Frangioni JV. Sentinel lymph node mapping of the pleural space. Chest 2005; 127:1799–804

    Article  PubMed  Google Scholar 

  16. Parungo CP, Ohnishi S, Kim SW, et al. Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging. J Thorac Cardiovasc Surg 2005; 129:844–50

    Article  PubMed  Google Scholar 

  17. Soltesz EG, Kim S, Kim SW, et al. Sentinel lymph node mapping of the gastrointestinal tract by using invisible light. Ann Surg Oncol 2006; 13:386–96

    Article  PubMed  Google Scholar 

  18. Kim SW, Kim S, Tracy JB, Jasanoff A, Bawendi MG. Phosphine oxide polymer for water-soluble nanoparticles. J Am Chem Soc 2005; 127:4556–7

    Article  PubMed  CAS  Google Scholar 

  19. Kim S, Fisher B, Eisler HJ, Bawendi M. Type-II quantum dots: CdTe/CdSe(core/shell) and CdSe/ZnTe(core/shell) heterostructures. J Am Chem Soc 2003; 125:11466–7

    Article  PubMed  CAS  Google Scholar 

  20. Frangioni JV, Kim SW, Ohnishi S, Kim S, Bawendi MG. Sentinel lymph node mapping with type II quantum dots. Methods Mol Biol 2006; In Press

  21. Misfeldt ML, Grimm DR. Sinclair miniature swine: an animal model of human melanoma. Vet Immunol Immunopathol 1994; 43:167–75

    Article  PubMed  CAS  Google Scholar 

  22. Goldberg BB, Merton DA, Liu JB, Murphy G, Forsberg F. Contrast-enhanced sonographic imaging of lymphatic channels and sentinel lymph nodes. J Ultrasound Med 2005; 24:953–65

    PubMed  Google Scholar 

  23. Goldberg BB, Merton DA, Liu JB, et al. Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US. Radiology 2004; 230:727–34

    PubMed  Google Scholar 

  24. Kim SW, Zimmer JP, Ohnishi S, Tracy JB, Frangioni JV, Bawendi MG. Engineering InAs(x)P(1-x)/InP/ZnSe III-V alloyed core/shell quantum dots for the near-infrared. J Am Chem Soc 2005; 127:10526–32

    Article  PubMed  CAS  Google Scholar 

  25. Ntziachristos V, Bremer C, Weissleder R. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur Radiol 2003; 13:195–208

    PubMed  Google Scholar 

  26. Sevick-Muraca EM, Houston JP, Gurfinkel M. Fluorescence-enhanced, near infrared diagnostic imaging with contrast agents. Curr Opin Chem Biol 2002; 6:642–50

    Article  PubMed  CAS  Google Scholar 

  27. Humblet V, Lapidus R, Williams LR, et al. High-affinity near-infrared fluorescent smallmolecule contrast agents for in vivo imaging of prostate-specific membrane antigen. Mol Imaging 2005; 4:448–62

    PubMed  Google Scholar 

  28. Frangioni JV. Translation of in vivo diagnostics from bench to bedside in the era of personalized medicine. Nat Biotechnol 2006; 24:909–13

    Article  PubMed  CAS  Google Scholar 

  29. Balacumaraswami L, Abu-Omar Y, Choudhary B, Pigott D, Taggart DP. A comparison of transit-time flowmetry and intraoperative fluorescence imaging for assessing coronary artery bypass graft patency. J Thorac Cardiovasc Surg 2005; 130:315–20

    Article  PubMed  Google Scholar 

  30. Sekijima M, Tojimbara T, Sato S, et al. An intraoperative fluorescent imaging system in organ transplantation. Transplant Proc 2004; 36:2188–90

    Article  PubMed  CAS  Google Scholar 

  31. Nakayama A, Bianco AC, Zhang CY, Lowell BB, Frangioni JV. Quantitation of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging. Mol Imaging 2003; 2:37–49

    Article  PubMed  Google Scholar 

  32. Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K. Crystal structure of human serum albumin at 2.5 A resolution. Protein Eng 1999; 12:439–46

    Article  PubMed  CAS  Google Scholar 

  33. Petitpas I, Bhattacharya AA, Twine S, East M, Curry S. Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I. J Biol Chem 2001; 276:22804–9

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Rita G. Laurence for assistance with animal anesthesia, Alec M. De Grand for maintenance of imaging system software, Daniel A. Brown for cryo-sectioning, Barbara L. Clough for editing, and Grisel Vasquez for administrative assistance. This work was supported in part by the National Science Foundation-Materials Research Science and Engineering Center Program under grant DMR-0213282 (MGB), NIH grants #R01-CA-115296 (JVF), R21-CA- 110185 (JVF), and R33-EB-000673 (JVF and MGB), and an Application Development Award (JVF) from the Center for Integration of Medicine and Innovative Technology (CIMIT).

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA

    Eiichi Tanaka MD, PhD, Hak Soo Choi PhD, Hirofumi Fujii MD, PhD & John V. Frangioni MD, PhD

  2. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Moungi G. Bawendi PhD

  3. Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA

    John V. Frangioni MD, PhD

  4. Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Room SL-B05, Boston, MA, 02215, USA

    John V. Frangioni MD, PhD

Authors
  1. Eiichi Tanaka MD, PhD
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  2. Hak Soo Choi PhD
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  3. Hirofumi Fujii MD, PhD
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  4. Moungi G. Bawendi PhD
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  5. John V. Frangioni MD, PhD
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Corresponding author

Correspondence to John V. Frangioni MD, PhD.

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Tanaka, E., Choi, H.S., Fujii, H. et al. Image-Guided Oncologic Surgery Using Invisible Light: Completed Pre-Clinical Development for Sentinel Lymph Node Mapping. Ann Surg Oncol 13, 1671–1681 (2006). https://doi.org/10.1245/s10434-006-9194-6

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  • DOI: https://doi.org/10.1245/s10434-006-9194-6

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