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Fluorescence-guided surgery with live molecular navigation — a new cutting edge

Nature Reviews Cancer volume 13, pages 653–662 (2013)Cite this article

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Abstract

A glowing new era in cancer surgery may be dawning. Using fluorescently labelled markers, surgical molecular navigation means that tumours and nerves can be displayed in real time intra-operatively in contrasting pseudocolours, which allows more complete tumour resection while preserving important structures. These advances can potentially cause a paradigm shift in cancer surgery, improving patient outcome and decreasing overall health-care costs.

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Figure 1: Live molecular detection of surgical margins.
Figure 2: Live molecular detection of nerves.

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Acknowledgements

The authors would like to thank S. Howell and L. Simon for helpful discussions on the regulatory aspects discussed in this manuscript, and M. Whitney for helpful scientific discussions.

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Authors and Affiliations

  1. The Division of Otolaryngology — Head and Neck Surgery, University of California at San Diego, La Jolla, 92093–0647, California, USA

    Quyen T. Nguyen

  2. The Department of Pharmacology, Howard Hughes Medical Institute, University of California at San Diego, La Jolla, 92093–0647, California, USA

    Roger Y. Tsien

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  1. Quyen T. Nguyen
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  2. Roger Y. Tsien
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Correspondence to Quyen T. Nguyen or Roger Y. Tsien.

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Glossary

Approved

An approved drug is a drug that has been authorized for a therapeutic use by a ruling authority. In Europe, the European Medicines Agency (EMA) is the ruling authority. In the United States, the Food and Drug Administration (FDA), an agency within the Department of Health and Human Services, provides this approval. A list of FDA-approved drugs is updated regularly on the FDA Orange Book website (see Further information).

Autofluorescence

Fluorescence that is inherent to different tissues (such as muscle, fat or liver) in the absence of any exogenously applied compounds.

Chlorotoxin

A peptide that is found in the venom of the scorpion Leiurus quinquestriatus that blocks small-conductance chloride channels. Chlorotoxin binds preferentially to gliomas and tumours of neuroectodermal origin.

Indication

A drug is approved by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for certain uses or indications following approved Phase I, II and III clinical trials. These indications are supplied with the package inserts for the drugs.

Infrared reflectivity

The fraction of incident infrared light that is reflected, which can vary between different tissues.

Intratumour microheterogeneity

The idea that within a given neoplasm, different tumour cells may display differences in genetic mutations and/or protein expression that may confer advantages and disadvantages for metastatic potential or response to chemotherapy or radiotherapy.

Lymphoedema

A condition of localized fluid retention and tissue swelling caused by a compromised lymphatic system. Lymphoedema is a common consequence of lymph node removal (for example, during neck dissection or axillary lymph node dissection) in the surgical treatment of cancer.

Medical device

An instrument that is used to diagnose or treat disease or other medical conditions and that does not achieve its purpose through chemical action within or on the body. In the United States, the Food and Drug Administration (FDA) is responsible for medical device evaluation, through premarket evaluation (510(k)) to show similarity with a previously approved device or through premarket approval (PMA) applications. PMA approval for a new device is based on a determination by the FDA that the PMA contains sufficient valid scientific evidence to ensure that the device is safe and effective for its intended use or uses.

Micro-anatomical cyto-architecture

The shapes and sizes of cells, nuclei, organelles and extracellular structures, which are used to distinguish tumour from normal tissue at microscopic resolution.

Nonspecific hydrophobic stickiness

Nonspecific binding to tissue of hydrophobic molecules such as most near-infrared dyes (which emit at wavelengths >700nm), thus typically resulting in increased background fluorescence.

Off-label

The clinical practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, at an unapproved dose or through an unapproved form of administration. After a drug has been approved for one purpose, licensed physicians are able to prescribe it for other purposes that in their professional judgment are both safe and effective, and are not limited to the official, approved indications.

Open-field surgery

A type of surgery in which the surgeon's view of the patient's tissue is through direct visualization through a large skin incision. This is in contrast to minimally invasive surgery (that is, laparoscopic surgery, endoscopic surgery or robotic surgery) in which the surgeon views the patient's tissues through fibre-optic probes or cameras, which are inserted through natural orifices or small skin incisions and the images are displayed on a computer screen.

Quantum dots

Inorganic nanocrystals that typically have a diameter of 2–8 nm. Most are composed of an inner semiconductor core of CdSe, an outer shell of ZnS, and an organic coating to make the quantum dot biocompatible. Quantum dots can be engineered to emit fluorescent light in the ultraviolet to infrared spectrum by varying their size.

Raman scattering

A spectroscopic technique that differentiates different tissue types depending on the infrared spectra of different molecules (such as fat and collagen) within that tissue.

Ratiometric imaging

Measurement of the ratio of fluorescence intensities at two wavelengths. When the response of the fluorescent probe to the desired signal (for example, protease activity) is markedly different at two wavelengths, calculating the ratio of the fluorescence at those wavelengths isolates the desired signal from confounding factors such as the absolute concentration of the fluorescent probe, the thickness of tissue, the intensity of illumination and the sensitivity of detection, which all affect intensities at both wavelengths by equal proportions. Ratiometric activatable cell-penetrating peptides (RACPPs)40 use pairs of dyes such as Cy5 and Cy7 as donor and acceptor dyes for fluorescence resonance energy transfer, thus enabling emission ratiometric discrimination of protease activity.

Sentinel lymph node

(SLN). The first draining lymph node for a given anatomical site. For breast cancer, the SLNs are located in the axilla.

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Nguyen, Q., Tsien, R. Fluorescence-guided surgery with live molecular navigation — a new cutting edge. Nat Rev Cancer 13, 653–662 (2013). https://doi.org/10.1038/nrc3566

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