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Tumor Endothelial Marker Imaging in Melanomas Using Dual-Tracer Fluorescence Molecular Imaging

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Abstract

Purpose

Cancer-specific endothelial markers available for intravascular binding are promising targets for new molecular therapies. In this study, a molecular imaging approach of quantifying endothelial marker concentrations (EMCI) is developed and tested in highly light-absorbing melanomas. The approach involves injection of targeted imaging tracer in conjunction with an untargeted tracer, which is used to account for nonspecific uptake and tissue optical property effects on measured targeted tracer concentrations.

Procedures

Theoretical simulations and a mouse melanoma model experiment were used to test out the EMCI approach. The tracers used in the melanoma experiments were fluorescently labeled anti-Plvap/PV1 antibody (plasmalemma vesicle associated protein Plvap/PV1 is a transmembrane protein marker exposed on the luminal surface of endothelial cells in tumor vasculature) and a fluorescent isotype control antibody, the uptakes of which were measured on a planar fluorescence imaging system.

Results

The EMCI model was found to be robust to experimental noise under reversible and irreversible binding conditions and was capable of predicting expected overexpression of PV1 in melanomas compared to healthy skin despite a 5-time higher measured fluorescence in healthy skin compared to melanoma: attributable to substantial light attenuation from melanin in the tumors.

Conclusions

This study demonstrates the potential of EMCI to quantify endothelial marker concentrations in vivo, an accomplishment that is currently unavailable through any other methods, either in vivo or ex vivo.

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Acknowledgments

This work was sponsored by NIH research grants R01 CA109558, U54 CA151662, and R21 CA175592, as well as a CIHR Postdoctoral Fellowship for KMT.

Conflict of Interest

There were no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, 60616, USA

    Kenneth M. Tichauer

  2. Department of Pathology, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA

    Sophie J. Deharvengt & Radu V. Stan

  3. Department of Surgery, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA

    Kimberley S. Samkoe & Brian W. Pogue

  4. Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA

    Mary-Jo Turk & Radu V. Stan

  5. Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA

    Kimberley S. Samkoe, Jason R. Gunn & Brian W. Pogue

  6. Biological and Biomedical Sciences, Yale University, New Haven, CT, 06520, USA

    Marcus W. Bosenberg

  7. Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03756, USA

    Mary-Jo Turk & Brian W. Pogue

  8. Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, 02114, USA

    Tayyaba Hasan & Brian W. Pogue

Authors
  1. Kenneth M. Tichauer
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  2. Sophie J. Deharvengt
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  3. Kimberley S. Samkoe
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Corresponding author

Correspondence to Kenneth M. Tichauer.

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Biological Sciences: Medical Sciences

Physical Sciences: Engineering

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Tichauer, K.M., Deharvengt, S.J., Samkoe, K.S. et al. Tumor Endothelial Marker Imaging in Melanomas Using Dual-Tracer Fluorescence Molecular Imaging. Mol Imaging Biol 16, 372–382 (2014). https://doi.org/10.1007/s11307-013-0692-1

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  • DOI: https://doi.org/10.1007/s11307-013-0692-1

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