Fluorescently labeled therapeutic antibodies for detection of microscopic melanoma
- 24 April 2013
- journal article
- research article
- Published by Wiley in The Laryngoscope
- Vol. 123 (11), 2681-2689
- https://doi.org/10.1002/lary.24102
Abstract
Objectives/Hypothesis Detection of microscopic disease during surgical resection of melanoma remains a significant challenge. To assess real‐time optical imaging for visualization of microscopic cancer, we evaluated three US Food and Drug Administration (FDA)‐approved therapeutic monoclonal antibodies. Study Design Prospective, basic science. Methods Melanoma cell lines (A375 and SKMEL5) were xenografted into the ears of immunodeficient mice. Bevacizumab, panitumumab, tocilizumab, or a nonspecific immunoglobin G (IgG) were covalently linked to a near‐infrared (NIR) fluorescent probe (IRDye800CW) and systemically injected. Primary tumors were imaged and then resected under fluorescent guidance using the SPY (Novadaq, Toronto, Ontario, Canada), an NIR imaging system used in plastic and reconstructive surgeries to evaluate perfusion. Mice were also imaged with the Pearl Impulse small animal imager (LI‐COR Biosciences, Lincoln, NE), an NIR imaging system designed for use with IRDye800CW. Postresection, small tissue fragments were fluorescently imaged and the presence of tumor subsequently confirmed by correlation with histology. Results All fluorescently labeled therapeutic monoclonal antibodies could adequately delineate tumor from normal tissue based on tumor‐to‐background ratios (TBR) compared to IgG‐IRDye800CW. On serial imaging, panitumumab achieved the highest TBRs with both SPY and Pearl (3.8 and 6.6, respectively). When used to guide resections, the antibody‐dye conjugates generated TBRs in the range of 1.3 to 2.2 (average, 1.6) using the SPY and 1.9 to 6.3 (average, 2.7) using the Pearl. There was no significant difference among the antibodies with either imaging modality or cell line (one‐way analysis of variance). Conclusions Our data suggest that FDA‐approved antibodies may be suitable targeting agents for the intraoperative fluorescent detection of melanoma. Laryngoscope, 123:2681–2689, 2013Keywords
This publication has 35 references indexed in Scilit:
- Intraoperative laser angiography using the SPY system: review of the literature and recommendations for useAnnals of Surgical Innovation and Research, 2013
- Use of Panitumumab-IRDye800 to Image Microscopic Head and Neck Cancer in an Orthotopic Surgical ModelAnnals of Surgical Oncology, 2012
- Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomasWorld Journal of Clinical Oncology, 2012
- Feasibility of Sentinel Node Biopsy in Head and Neck Melanoma Using a Hybrid Radioactive and Fluorescent TracerAnnals of Surgical Oncology, 2011
- Targeted, Activatable, In Vivo Fluorescence Imaging of Prostate-Specific Membrane Antigen (PSMA) Positive Tumors Using the Quenched Humanized J591 Antibody–Indocyanine Green (ICG) ConjugateBioconjugate Chemistry, 2011
- Current and Future Clinical Applications for Optical Imaging of Cancer: From Intraoperative Surgical Guidance to Cancer ScreeningSeminars in Oncology, 2011
- Optical Image-guided Surgery—Where Do We Stand?Molecular Imaging & Biology, 2010
- Single-Dose Intravenous Toxicity Study of IRDye 800CW in Sprague-Dawley RatsMolecular Imaging & Biology, 2010
- Interleukin and interleukin receptor gene polymorphisms and susceptibility to melanomaMelanoma Research, 2008
- Affibody Molecules for In vivo Characterization of HER2-Positive Tumors by Near-Infrared ImagingClinical Cancer Research, 2008