Evaluation of fluorescence-guided surgery agents in a murine model of soft tissue fibrosarcoma

J Surg Oncol. 2018 May;117(6):1179-1187. doi: 10.1002/jso.24950. Epub 2017 Dec 28.

Abstract

Background and objectives: Soft tissue sarcomas (STS) are mesenchymal malignancies. Treatment mainstay is surgical resection with negative margins ± adjuvant treatment. Fluorescence-guided surgical (FGS) resection can delineate intraoperative margins; FGS has improved oncologic outcomes in other malignancies. This novel strategy may minimize resection-associated morbidity while improving local tumor control.

Methods: We evaluate the tumor-targeting specificity and utility of fluorescence-imaging agents to provide disease-specific contrast. Mice with HT1080 fibrosarcoma tumors received one of five probes: cetuximab-IRDye800CW (anti-EGFR), DC101-IRDye800CW (anti-VEGFR-2), IgG-IRDye800CW, the cathepsin-activated probe Prosense750EX, or the small molecule probe IntegriSense750. Tumors were imaged daily using open- and closed-field fluorescence imaging systems. Tumor-to-background ratios (TBR) were evaluated. On peak TBR days, probe sensitivity was evaluated. Tumors were stained and imaged microscopically.

Results: At peak, closed-field imaging TBR of cetuximab-IRDye800CW (16.8) was significantly greater (P < 0.0001) than Integrisense750 (7.0), Prosense750EX (5.8), and DC101-IRDye800CW (3.7). All agents successfully localized as little as 1.0 mg of tumor tissue in the post-resection bed; cetuximab-IRDye800CW generated the greatest contrast (2.5). Cetuximab-IRDye800CW revealed strong tumor affinity microscopically; tumor fluorescence intensity was significantly greater (P < 0.0004) than 0.2 mm away from tumor border.

Conclusion: This study demonstrates cetuximab-IRDye800CW superiority. FGS has the potential to improve post-resection morbidity and mortality by improving disease detection.

Keywords: fibrosarcoma; fluorescence; optical guided surgery; soft tissue sarcoma; surgical oncology.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism*
  • Female
  • Fibrosarcoma / diagnostic imaging
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / pathology
  • Fibrosarcoma / surgery*
  • Fluorescent Dyes / metabolism*
  • Mice
  • Mice, Nude
  • Optical Imaging / methods*
  • Sarcoma, Experimental / diagnostic imaging
  • Sarcoma, Experimental / metabolism
  • Sarcoma, Experimental / pathology
  • Sarcoma, Experimental / surgery*
  • Surgery, Computer-Assisted / methods*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Fluorescent Dyes