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01-08-2017 | Research Article

Effects of an Unlabeled Loading Dose on Tumor-Specific Uptake of a Fluorescently Labeled Antibody for Optical Surgical Navigation

Authors: Lindsay S. Moore, Eben L. Rosenthal, Esther de Boer, Andrew C. Prince, Neel Patel, Joshua M. Richman, Anthony B. Morlandt, William R. Carroll, Kurt R. Zinn, Jason M. Warram

Published in: Molecular Imaging and Biology | Issue 4/2017

Abstract

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.

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Title: Effects of an Unlabeled Loading Dose on Tumor-Specific Uptake of a Fluorescently Labeled Antibody for Optical Surgical Navigation
Authors: Lindsay S. Moore
Eben L. Rosenthal
Esther de Boer
Andrew C. Prince
Neel Patel
Joshua M. Richman
Anthony B. Morlandt
William R. Carroll
Kurt R. Zinn
Jason M. Warram
Publication date: 01-08-2017
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 4/2017
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-016-1022-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of an Unlabeled Loading Dose on Tumor-Specific Uptake of a Fluorescently Labeled Antibody for Optical Surgical Navigation

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

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