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Published on: July 17, 2012
Effects of an Unlabeled Loading Dose on Tumor-Specific Uptake of a Fluorescently Labeled Antibody for Optical
Lindsay S Moore1, Eben L Rosenthal2, Esther de Boer1,3
1Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA.
Purpose:
Intraoperative optical imaging to guide surgeons during oncologic resections offers a unique and promising solution to the ambiguity of cancer margins to tactile and visual assessment that results in devastatingly high rates of positive margins. Sequestering of labeled antibodies by normal tissues with high expression of the antibody target, or "antigen sinks", diminishes the efficacy of these probes to provide contrast between the tumor and background tissues by decreasing the amount of circulating probe available for uptake by the tumor and by increasing the fluorescence of non-tumor tissues. We hypothesized that administering a dose of unlabeled antibody prior to infusion of the near-infrared (NIR) fluorescently labeled antibody would improve tumor-specific uptake and contrast of the fluorescently labeled probe by occupying extra-tumoral binding sites, thereby increasing the amount of labeled probe available for uptake by the tumor.
Procedures:
In this study, we explore this concept by testing two different "pre-load" doses of unlabeled cetuximab (the standard 10-mg test dose, and a larger, experimental 100-mg test dose) in six patients receiving cetuximab conjugated to the fluorescent dye IRDye800CW (cetuximab-IRDye800CW) in a clinical trial, and compared the amount of fluorescent antibody in tumor and background tissues, as well as the tumor-specific contrast of each.
Results:
The patients receiving the larger preload (100 mg) of unlabeled cetuximab demonstrated significantly higher concentrations (9.5 vs. 0.1 μg) and a longer half-life (30.3 vs. 20.6 days) of the labeled cetuximab in plasma, as well as significantly greater tumor fluorescence (32.3 vs. 9.3 relative fluorescence units) and tumor to background ratios (TBRs) (5.5 vs. 1.7).
Conclusions:
Administering a preload of unlabeled antibody prior to infusion of the fluorescently labeled drug may be a simple and effective way to improve the performance of antibody-based probes to guide surgical resection of solid malignancies.
Insights
A pre-load dose of unlabeled antibody improves near-infrared fluorescent imaging for cancer surgery. This method enhances tumor contrast and probe uptake, aiding surgeons in identifying cancer margins more effectively.
Area of Science:
- Oncology
- Medical Imaging
- Pharmacology
Background:
- Intraoperative optical imaging is crucial for guiding oncologic resections and improving cancer margin assessment.
- High rates of positive margins persist due to limitations in current visual and tactile assessments.
- Antibody-based probes can be hindered by 'antigen sinks' in normal tissues, reducing tumor contrast.
Purpose of the Study:
- To investigate if a pre-load dose of unlabeled antibody can improve tumor-specific uptake and contrast of near-infrared (NIR) fluorescently labeled antibodies.
- To determine if occupying extra-tumoral binding sites enhances the efficacy of fluorescent probes for cancer surgery.
Main Methods:
- A clinical trial involving six patients undergoing treatment with cetuximab conjugated to IRDye800CW (cetuximab-IRDye800CW).
- Testing two pre-load doses of unlabeled cetuximab: a standard 10-mg dose and an experimental 100-mg dose.
- Comparing fluorescence levels in tumor and background tissues, and calculating tumor-to-background ratios (TBRs).
Main Results:
- Patients receiving the 100-mg pre-load dose showed significantly higher concentrations (9.5 vs. 0.1 μg) and longer half-life (30.3 vs. 20.6 days) of labeled cetuximab in plasma.
- The 100-mg pre-load group exhibited significantly greater tumor fluorescence (32.3 vs. 9.3 RFU) and improved TBRs (5.5 vs. 1.7).
Conclusions:
- Administering a pre-load of unlabeled antibody is a simple and effective strategy.
- This method enhances the performance of antibody-based probes for guiding surgical resection of solid malignancies.
- Improved tumor contrast and probe uptake facilitate better identification of cancer margins during surgery.
