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  • Review Article
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NIR-II light in clinical oncology: opportunities and challenges

Nature Reviews Clinical Oncology (2024)Cite this article

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Abstract

Novel strategies utilizing light in the second near-infrared region (NIR-II; 900–1,880 nm wavelengths) offer the potential to visualize and treat solid tumours with enhanced precision. Over the past few decades, numerous techniques leveraging NIR-II light have been developed with the aim of precisely eliminating tumours while maximally preserving organ function. During cancer surgery, NIR-II optical imaging enables the visualization of clinically occult lesions and surrounding vital structures with increased sensitivity and resolution, thereby enhancing surgical quality and improving patient prognosis. Furthermore, the use of NIR-II light promises to improve cancer phototherapy by enabling the selective delivery of increased therapeutic energy to tissues at greater depths. Initial clinical studies of NIR-II-based imaging and phototherapy have indicated impressive potential to decrease cancer recurrence, reduce complications and prolong survival. Despite the encouraging results achieved, clinical translation of innovative NIR-II techniques remains challenging and inefficient; multidisciplinary cooperation is necessary to bridge the gap between preclinical research and clinical practice, and thus accelerate the translation of technical advances into clinical benefits. In this Review, we summarize the available clinical data on NIR-II-based imaging and phototherapy, demonstrating the feasibility and utility of integrating these technologies into the treatment of cancer. We also introduce emerging NIR-II-based approaches with substantial potential to further enhance patient outcomes, while also highlighting the challenges associated with imminent clinical studies of these modalities.

Key points

  • Extending the clinical imaging spectrum to the second near-infrared (NIR-II) window offers greatly improved visualization of multiple features of cancer, providing a promising approach for enhancing surgical quality and facilitating oncological research.

  • The efficacy of phototherapy can be substantially improved through the use of NIR-II irradiation, with the potential to improve therapeutic selectivity for cancer and facilitate the development of innovative combination therapies.

  • Early phase clinical studies of NIR-II image-guided surgery and phototherapy for solid tumours have demonstrated promising potential to improve resection rates, reduce complications and prolong survival.

  • Facilitating clinical application will be the primary objective for the future development of NIR-II techniques; a cyclical flow from bench to bedside and back again is necessary to promote this clinical translation.

  • Emerging NIR-II techniques should aim to complement and enhance existing approaches rather than replace them; exploiting incremental value is essential to translating these novel approaches into clinical practice.

  • Advances in NIR-II techniques might greatly facilitate a paradigm shift in cancer imaging, surgery and phototherapy, ultimately improving patient outcomes.

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Fig. 1: Fundamental principles and applications of NIR-II imaging and phototherapy.
Fig. 2: Key advances in NIR-II imaging and phototherapy of cancer.
Fig. 3: NIR-II image-guided surgery and PTT.

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Acknowledgements

The authors acknowledge grant support from the National Natural Science Foundation of China (62027901, 81930053 and 81227901 to J. Tian, 92359301 to J.D., 92259302 to J.J., 92259303 to J.W., 92059207 to Z.H.) and the CAS Youth Interdisciplinary Team (JCTD-2021-08 to Z.H.), as well as research support from the National Key Laboratory of Kidney Diseases (China).

Author information

Author notes

  1. These authors contributed equally: Zeyu Zhang, Yang Du, Xiaojing Shi.

Authors and Affiliations

  1. Key Laboratory of Big Data-Based Precision Medicine of Ministry of Industry and Information Technology, School of Engineering Medicine, Beihang University, Beijing, China

    Zeyu Zhang & Jie Tian

  2. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Chinese Academy of Sciences, Beijing, China

    Yang Du, Xiaojing Shi, Kun Wang, Qian Liang, Kunshan He, Chongwei Chi, Zhenhua Hu & Jie Tian

  3. Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan, China

    Qiaojun Qu

  4. School of Control Science and Engineering, Shandong University, Jinan, China

    Xiaopeng Ma

  5. Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Jianqiang Tang

  6. Department of General Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Bo Liu

  7. Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, China

    Jiafu Ji

  8. Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People’s Hospital, Beijing, China

    Jun Wang

  9. Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

    Jiahong Dong

  10. Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, China

    Jie Tian

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  1. Zeyu Zhang
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  12. Jiafu Ji
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  13. Jun Wang
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  14. Jiahong Dong
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  15. Zhenhua Hu
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  16. Jie Tian
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Contributions

Z.Z., Y.D. and X.S. researched data for the article and wrote the manuscript. All authors made a substantial contribution to discussions of content and reviewed and/or edited the manuscript prior to submission.

Corresponding authors

Correspondence to Jiafu Ji, Jun Wang, Jiahong Dong, Zhenhua Hu or Jie Tian.

Peer review

Peer review information

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

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The authors declare no competing interests.

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Glossary

Aggregation-induced emission

A photophysical phenomenon whereby certain organic fluorescent dyes have enhanced electron-donating and donor–acceptor abilities and, thus, increased emission efficiency when aggregated compared to when they are in a dispersed state.

Ambient interference

Background fluorescence originating from sources outside the field of view; for example, the reflected light from shadowless lamps and the light emitted by nearby light-emitting diode monitors.

Autofluorescence

Intrinsic emission of light by biological structures when excited by external light, primarily within the visible spectrum.

Back-table imaging systems

Imaging systems typically comprising a lightproof imaging chamber and movable frame, intended for pathological examination of fresh tissue samples in the operating room during the surgical procedure.

Cerenkov radiation

A form of electromagnetic energy emitted by charged subatomic particles travelling faster than light in a dielectric medium such as biological tissue.

Enhanced permeability and retention

Phenomenon in which non-targeted high molecular weight compounds accumulate in tissues with high levels of vascular permeability, such as tumours with a characteristically abnormal vasculature.

Lifetime imaging

A quantitative imaging approach that captures and analyses the duration of fluorescence emission.

Maximum permissible exposure

The highest power or energy density of a light source that is considered safe, with negligible probability of causing damage to the eye or skin.

Open-field imaging systems

Imaging systems tailored for use during open surgery, enhancing visualization of tissues with decimetre-scale size of the field of view and metres-long working distances.

Photoacoustic imaging

A biomedical imaging modality that utilizes the photoacoustic effect to produce wideband ultrasonic emission through transient thermoelastic expansion, and that is expected to combine the strengths of deep ultrasound penetration with high optical contrast.

Photon scattering

During bio-optical imaging, scattering occurs when the directional motion of photons is altered owing to their interaction with tissue or other materials, potentially affecting image quality and imaging depth.

Pyrolysis

The thermal decomposition of materials, often in an inert atmosphere, resulting in volatile products.

Quantum yield

The ratio of the number of photons emitted relative to the number of photons absorbed.

Quenching

Decreased fluorescence intensity owing to various features of fluorophores, such as excited state reactions, energy transfer, complex formation and collisional deactivation.

Ratiometric imaging

An imaging method that involves measuring fluorescence intensities at multiple emission wavelengths, which can differ under different physiological conditions, to monitor changes in the surrounding tissue microenvironment.

Ultrasound-triggered cavitation

Phenomenon in which high-frequency sound waves create tiny bubbles in a liquid, which then rapidly collapse, releasing energy.

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Cite this article

Zhang, Z., Du, Y., Shi, X. et al. NIR-II light in clinical oncology: opportunities and challenges. Nat Rev Clin Oncol (2024). https://doi.org/10.1038/s41571-024-00892-0

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