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Published on: September 19, 2014
Evaluation of fluorescence-guided surgery agents in a murine model of soft tissue fibrosarcoma
Andrew C Prince1, Andrew S McGee1, Herrick Siegel2
1University of Alabama School of Medicine, Birmingham, Alabama.
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.
Insights
Cetuximab-IRDye800CW demonstrates superior tumor targeting for soft tissue sarcoma (STS) detection. Fluorescence-guided surgery (FGS) using this agent may improve outcomes by enhancing intraoperative margin delineation and reducing resection-associated morbidity.
Area of Science:
- Oncology
- Surgical Oncology
- Medical Imaging
Background:
- Soft tissue sarcomas (STS) are mesenchymal malignancies requiring surgical resection.
- Achieving negative margins is crucial for optimal oncologic outcomes.
- Fluorescence-guided surgery (FGS) offers potential for improved margin delineation and reduced morbidity.
Purpose of the Study:
- To evaluate the tumor-targeting specificity and utility of novel fluorescence-imaging agents for STS.
- To determine the efficacy of different probes in providing disease-specific contrast for intraoperative margin assessment.
- To assess the potential of FGS to improve local tumor control and minimize resection-associated morbidity.
Main Methods:
- Mice bearing HT1080 fibrosarcoma tumors were administered one of five fluorescence probes: cetuximab-IRDye800CW, DC101-IRDye800CW, IgG-IRDye800CW, Prosense750EX, or IntegriSense750.
- Tumors were imaged daily using open- and closed-field fluorescence imaging systems to evaluate tumor-to-background ratios (TBR).
- Probe sensitivity and microscopic tumor affinity were assessed on peak TBR days.
Main Results:
- Cetuximab-IRDye800CW achieved a significantly greater peak TBR (16.8) in closed-field imaging compared to other agents.
- All agents detected as little as 1.0 mg of residual tumor, with cetuximab-IRDye800CW providing the highest contrast (2.5).
- Microscopic analysis confirmed strong tumor affinity for cetuximab-IRDye800CW, with fluorescence intensity significantly higher within 0.2 mm of the tumor border.
Conclusions:
- Cetuximab-IRDye800CW demonstrated superior tumor-targeting specificity and contrast among the evaluated agents.
- FGS utilizing cetuximab-IRDye800CW holds promise for enhancing disease detection during surgery.
- This approach has the potential to improve post-resection outcomes by reducing morbidity and mortality.
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