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Fundamentals and developments in fluorescence-guided cancer surgery

Abstract

Fluorescence-guided surgery using tumour-targeted imaging agents has emerged over the past decade as a promising and effective method of intraoperative cancer detection. An impressive number of fluorescently labelled antibodies, peptides, particles and other molecules related to cancer hallmarks have been developed for the illumination of target lesions. New approaches are being implemented to translate these imaging agents into the clinic, although only a few have made it past early-phase clinical trials. For this translational process to succeed, target selection, imaging agents and their related detection systems and clinical implementation have to operate in perfect harmony to enable real-time intraoperative visualization that can benefit patients. Herein, we review key aspects of this imaging cascade and focus on imaging approaches and methods that have helped to shed new light onto the field of intraoperative fluorescence-guided cancer surgery with the singular goal of improving patient outcomes.

Key points

  • Tumour-targeted fluorescence-guided surgery (FGS) has emerged as a promising technique for the intraoperative visualization of solid tumours.

  • Different approaches can be used to make imaging agents specifically bind to or interact with a target protein associated with a cancer hallmark.

  • Imaging systems for clinical tumour-targeted FGS are available and provide real-time qualitative images.

  • Phase III studies are currently ongoing to prove patient benefit from tumour-targeted FGS.

  • Future camera developments focus on the quantification of fluorescence imaging by correcting for an array of optical properties.

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Fig. 1: Important stages in the development and clinical translation of tumour-targeted imaging agents.
Fig. 2: Timeline of seminal discoveries leading to the development of tumour-targeted fluorescence-guided surgery.
Fig. 3: Overview of approaches to enable tumour-targeted imaging.
Fig. 4: Effect of photon and tissue properties in qualitative output in clinical fluorescence imaging.

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Acknowledgements

The authors would like to thank Dr J.H. van Dierendonck for his artistic contribution to this article. The authors received support from the Dutch Cancer Society (KWF; young investigator grant 11289 to R.J.S.), the Dutch Organization for Scientific Research (NWO; Veni grant 016.196.059 to J.S.D.M.) and the European Commission H2020-MSCA-ITN-2019 (project number: 857894 – CAST to A.L.V.).

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Many of the topics discussed in this Review were studied and described by Dr Sanjiv S. Gambhir, one of the founders of molecular imaging, who unfortunately passed away during the preparation of this manuscript in July 2020. We thank him for his exceptional mentorship and forward-looking vision.

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Nature Reviews Clinical Oncology thanks M. Bouvet, J. Warram and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Mieog, J.S.D., Achterberg, F.B., Zlitni, A. et al. Fundamentals and developments in fluorescence-guided cancer surgery. Nat Rev Clin Oncol (2021). https://doi.org/10.1038/s41571-021-00548-3

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