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Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy

Author

Listed:
  • Gregory T. Kennedy

    (University of Pennsylvania School of Medicine)

  • Feredun S. Azari

    (University of Pennsylvania School of Medicine)

  • Elizabeth Bernstein

    (University of Pennsylvania School of Medicine)

  • Bilal Nadeem

    (University of Pennsylvania School of Medicine)

  • Ashley Chang

    (University of Pennsylvania School of Medicine)

  • Alix Segil

    (University of Pennsylvania School of Medicine)

  • Sean Carlin

    (University of Pennsylvania School of Medicine)

  • Neil T. Sullivan

    (University of Pennsylvania School of Medicine)

  • Emmanuel Encarnado

    (University of Pennsylvania School of Medicine)

  • Charuhas Desphande

    (University of Pennsylvania School of Medicine)

  • Sumith Kularatne

    (On Target Laboratories)

  • Pravin Gagare

    (On Target Laboratories)

  • Mini Thomas

    (On Target Laboratories)

  • John C. Kucharczuk

    (University of Pennsylvania School of Medicine)

  • Gaetan Christien

    (Mauna Kea Technologies)

  • Francois Lacombe

    (Mauna Kea Technologies)

  • Kaela Leonard

    (Mauna Kea Technologies)

  • Philip S. Low

    (Purdue University)

  • Aline Criton

    (Mauna Kea Technologies)

  • Sunil Singhal

    (University of Pennsylvania School of Medicine)

Abstract

Suspicious nodules detected by radiography are often investigated by biopsy, but the diagnostic yield of biopsies of small nodules is poor. Here we report a method—NIR-nCLE—to detect cancer at the cellular level in real-time during biopsy. This technology integrates a cancer-targeted near-infrared (NIR) tracer with a needle-based confocal laser endomicroscopy (nCLE) system modified to detect NIR signal. We develop and test NIR-nCLE in preclinical models of pulmonary nodule biopsy including human specimens. We find that the technology has the resolution to identify a single cancer cell among normal fibroblast cells when co-cultured at a ratio of 1:1000, and can detect cancer cells in human tumors less than 2 cm in diameter. The NIR-nCLE technology rapidly delivers images that permit accurate discrimination between tumor and normal tissue by non-experts. This proof-of-concept study analyzes pulmonary nodules as a test case, but the results may be generalizable to other malignancies.

Suggested Citation

  • Gregory T. Kennedy & Feredun S. Azari & Elizabeth Bernstein & Bilal Nadeem & Ashley Chang & Alix Segil & Sean Carlin & Neil T. Sullivan & Emmanuel Encarnado & Charuhas Desphande & Sumith Kularatne & P, 2022. "Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30265-z
    DOI: 10.1038/s41467-022-30265-z
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    References listed on IDEAS

    as
    1. Naoki Nishio & Nynke S. van den Berg & Stan van Keulen & Brock A. Martin & Shayan Fakurnejad & Nutte Teraphongphom & Stefania U. Chirita & Nicholas J. Oberhelman & Guolan Lu & Crista E. Horton & Micha, 2019. "Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Takahiro Kuchimaru & Satoshi Iwano & Masahiro Kiyama & Shun Mitsumata & Tetsuya Kadonosono & Haruki Niwa & Shojiro Maki & Shinae Kizaka-Kondoh, 2016. "A luciferin analogue generating near-infrared bioluminescence achieves highly sensitive deep-tissue imaging," Nature Communications, Nature, vol. 7(1), pages 1-8, September.
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