• William C Eward, Jeffrey K Mito, Cindy A Eward, Jessica E Carter, Jorge M Ferrer, David G Kirsch, and Brian E Brigman.
• Department of Orthopaedic Surgery, Duke University Medical Center, Box 3312 DUMC, Durham, NC 277710, USA. w.eward@alumni.duke.edu
• Clin. Orthop. Relat. Res. 2013 Mar 1; 471 (3): 834-42.

BackgroundTreatment 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/PurposesTo 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?MethodsWe 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).ResultsFluorescence was apparent from all 10 tumors and ranged from 3 × 10(7) to 1 × 10(9) counts/millisecond/cm(2). 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.ConclusionsThese initial findings suggest this imaging system might be useful to intraoperatively detect residual tumor after wide resections.Clinical RelevanceThe ability to assess the tumor bed intraoperatively for residual disease has the potential to improve local control.

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