Evaluation of Novel Imaging Devices for Nanoparticle-Mediated Fluorescence-Guided Lung Tumor Therapy

Tomonari Kinoshita, Hideki Ujiie, Juan Chen, Lili Ding, Harley Chan, Alexander Gregor, Nicholas Bernards, Patrick Z. McVeigh, Kosuke Fujino, Chang Young Lee, Yamato Motooka, Terunaga Inage, Michael S. Valic, Andrew Effat, Robert Weersink, Brian C. Wilson, Gang Zheng, Hisao Asamura, Kazuhiro Yasufuku

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1 Citation (Scopus)

Abstract

Background: Nonsurgical and minimally invasive approaches for early-stage peripheral lung cancer are needed to avoid the known morbidity of surgical resection, particularly in high-risk patients. We previously demonstrated the utility of multifunctional porphyrin-phospholipid nanoparticles (porphysomes) for fluorescence imaging and phototherapy after preferential accumulation into tumors. The objective of this study was to demonstrate the feasibility of porphysome-mediated imaging and photothermal therapy using a newly developed fiberscope and thoracoscope. Methods: To prepare this technology for clinical translation, we developed a porphysome-specific fiberscope (scanning fiber endoscope and porphysome-specific thoracoscope), both capable of detecting porphysome fluorescence, for image-guided transbronchial and transpleural photothermal therapy to treat endobronchial/peribronchial and subpleural tumors, respectively. These were tested in three animal models: human lung cancer xenografts (A549) in mice, orthotopic VX2 lung tumors in rabbits, and ex vivo pig lung into which A549 tumor tissue was transplanted. Results: The scanning fiber endoscope, with a 1.2-mm diameter, is small enough to pass through the working channel of a conventional bronchoscope and could visualize porphysome-laden tumors located inside or close to the peripheral bronchial wall. The porphysome-specific thoracoscope system had high sensitivity for porphysome fluorescence and enabled image-guided thoracoscopic resection of porphysome-accumulating tumors close to the pleura. Porphysomes also enhanced the efficacy of scanning fiber endoscope-guided transbronchial photothermal therapy and porphysome-specific thoracoscope-guided transpleural photothermal therapy, resulting in selective and efficient tumor tissue ablation in the rabbit and pig models. Conclusions: These results support the potential for clinical translation of this novel platform to affect nonsurgical and minimally invasive treatment options for early-stage peripheral lung cancer.

Original languageEnglish
JournalAnnals of Thoracic Surgery
DOIs
Publication statusPublished - 2019 Jan 1

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Kinoshita, T., Ujiie, H., Chen, J., Ding, L., Chan, H., Gregor, A., Bernards, N., McVeigh, P. Z., Fujino, K., Lee, C. Y., Motooka, Y., Inage, T., Valic, M. S., Effat, A., Weersink, R., Wilson, B. C., Zheng, G., Asamura, H., & Yasufuku, K. (2019). Evaluation of Novel Imaging Devices for Nanoparticle-Mediated Fluorescence-Guided Lung Tumor Therapy. Annals of Thoracic Surgery. https://doi.org/10.1016/j.athoracsur.2019.01.008