title: A novel imaging system permits real-time in vivo tumor bed assessment after resection of naturally occurring sarcomas in dogs.
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.
  
  
  OBJECTIVE
  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 × 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.
  
  
  CONCLUSIONS
  These initial findings suggest this imaging system might be useful to intraoperatively detect residual tumor after wide resections.
  
  
  CONCLUSIONS
  The ability to assess the tumor bed intraoperatively for residual disease has the potential to improve local control.
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Box 3312 DUMC, Durham, NC 277710, USA. w.eward@alumni.duke.edu
authors.forename: William C
authors.initials: WC
authors.lastname: Eward
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Mito
authors.forename: Cindy A
authors.initials: CA
authors.lastname: Eward
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Carter
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Ferrer
authors.forename: David G
authors.initials: DG
authors.lastname: Kirsch
authors.forename: Brian E
authors.initials: BE
authors.lastname: Brigman
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D004283:Dog Diseases / Q000601:surgery*; D004285:Dogs; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D057054:Molecular Imaging / Q000379:methods / Q000662:veterinary*; D009364:Neoplasm Recurrence, Local / Q000662:veterinary*; D018365:Neoplasm, Residual; D012509:Sarcoma / Q000098:blood supply / Q000201:enzymology / Q000601:surgery / Q000662:veterinary*; D012983:Soft Tissue Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000601:surgery / Q000662:veterinary*; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes; D002403:Cathepsins