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A Novel Imaging System Permits Real-time in Vivo Tumor Bed Assessment After Resection of Naturally Occurring Sarcomas in Dogs

  • Symposium: Highlights from the First Combined 2011 Meeting of the Musculoskeletal Tumor Society and Connective Tissue Oncology Society
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Treatment of soft tissue sarcoma (STS) includes complete tumor excision. However, in some patients, residual sarcoma cells remain in the tumor bed. We previously described a novel hand-held imaging device prototype that uses molecular imaging to detect microscopic residual cancer in mice during surgery.

Questions/purposes

To test this device in a clinical trial of dogs with naturally occurring sarcomas, we asked: (1) Are any adverse clinical or laboratory effects observed after intravenous administration of the fluorescent probes? (2) Do canine sarcomas exhibit fluorescence after administration of the cathepsin-activated probe? (3) Is the tumor-to-background ratio sufficient to distinguish tumor from tumor bed? And (4) can residual fluorescence be detected in the tumor bed during surgery and does this correlate with a positive margin?

Methods

We studied nine dogs undergoing treatment for 10 STS or mast cell tumors. Dogs received an intravenous injection of VM249, a fluorescent probe that becomes optically active in the presence of cathepsin proteases. After injection, tumors were removed by wide resection. The tumor bed was imaged using the novel imaging device to search for residual fluorescence. We determined correlations between tissue fluorescence and histopathology, cathepsin protease expression, and development of recurrent disease. Minimum followup was 9 months (mean, 12 months; range, 9–15 months).

Results

Fluorescence was apparent from all 10 tumors and ranged from 3 × 107 to 1 × 109 counts/millisecond/cm2. During intraoperative imaging, normal skeletal muscle showed no residual fluorescence. Histopathologic assessment of surgical margins correlated with intraoperative imaging in nine of 10 cases; in the other case, there was no residual fluorescence, but tumor was found at the margin on histologic examination. No animals had recurrent disease at 9 to 15 months.

Conclusions

These initial findings suggest this imaging system might be useful to intraoperatively detect residual tumor after wide resections.

Clinical Relevance

The ability to assess the tumor bed intraoperatively for residual disease has the potential to improve local control.

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Acknowledgments

The authors thank our collaborators Moungi Bawendi, PhD, Linda Griffith, PhD, and W. David Lee, MS, at the Massachusetts Institute of Technology for valuable discussions regarding experimental design and data interpretation. We also thank Gary Spodnick, DVM, Brian Trumpatori, DVM, David Russlander, DVM, Angie Kozicki, DVM, and Stephen Engler, DVM, the collaborators from the multidisciplinary small animal oncology team at Veterinary Specialty Hospital of the Carolinas.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Duke University Medical Center, Box 3312 DUMC, Durham, NC, 277710, USA

    William C. Eward DVM, MD

  2. Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC, USA

    Jeffrey K. Mito MD, PhD

  3. Veterinary Specialty Hospital of the Carolinas, Cary, NC, USA

    Cindy A. Eward DVM

  4. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA

    Jorge M. Ferrer PhD

  5. Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC, USA

    Jessica E. Carter & David G. Kirsch MD, PhD

  6. Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA

    Jessica E. Carter & David G. Kirsch MD, PhD

  7. Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA

    Brian E. Brigman MD, PhD

Authors
  1. William C. Eward DVM, MD
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  2. Jeffrey K. Mito MD, PhD
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  3. Cindy A. Eward DVM
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  4. Jessica E. Carter
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  5. Jorge M. Ferrer PhD
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  6. David G. Kirsch MD, PhD
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  7. Brian E. Brigman MD, PhD
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Corresponding author

Correspondence to William C. Eward DVM, MD.

Additional information

The institution of one or more of the authors has received funding, during the study period, from an NIH CTSA grant (UL1RR024128) from the Duke Translational Research Institute (BEB), the Damon Runyon-Rachleff Innovation Award (DGK), and a Fitzgerald Scholarship (JEC). Two of the authors (DGK and JMF) certify that they have received or may receive payments or benefits, during the study period, an amount of $10,000 to $100,000, from Lumicell Diagnostics, Inc (Waltham, MA, USA), a company commercializing in vivo imaging systems. Two of the authors (DGK and JMF) certify that they are members of the scientific advisory board for Lumicell Diagnostics, Inc.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at Duke University Medical Center (Durham, NC, USA) and the Veterinary Specialty Hospital of the Carolinas (Cary, NC, USA).

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Eward, W.C., Mito, J.K., Eward, C.A. et al. A Novel Imaging System Permits Real-time in Vivo Tumor Bed Assessment After Resection of Naturally Occurring Sarcomas in Dogs. Clin Orthop Relat Res 471, 834–842 (2013). https://doi.org/10.1007/s11999-012-2560-8

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  • DOI: https://doi.org/10.1007/s11999-012-2560-8

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