TY - JOUR
T1 - Evaluation of Novel Imaging Devices for Nanoparticle-Mediated Fluorescence-Guided Lung Tumor Therapy
AU - Kinoshita, Tomonari
AU - Ujiie, Hideki
AU - Chen, Juan
AU - Ding, Lili
AU - Chan, Harley
AU - Gregor, Alexander
AU - Bernards, Nicholas
AU - McVeigh, Patrick Z.
AU - Fujino, Kosuke
AU - Lee, Chang Young
AU - Motooka, Yamato
AU - Inage, Terunaga
AU - Valic, Michael S.
AU - Effat, Andrew
AU - Weersink, Robert
AU - Wilson, Brian C.
AU - Zheng, Gang
AU - Asamura, Hisao
AU - Yasufuku, Kazuhiro
N1 - Funding Information:
The authors wish to thank Ms Kimberley Hudson, Ms Patrycja Bauer, Ms Judy McConnell, and Ms Alexandria Grindlay (Toronto General Hospital) for laboratory management. This research was funded by the Canadian Cancer Society Research Institute (Grant #704123), the Terry Fox Research Institute (Grant #1075), and the Canadian Institute of Health Research (Grant #154326). The SFE system was supported by The Canadian Foundation for Innovation (Grant #33425) and the Princess Margaret Cancer Foundation.
Publisher Copyright:
© 2019 The Society of Thoracic Surgeons
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.athoracsur.2019.01.008
DO - 10.1016/j.athoracsur.2019.01.008
M3 - Article
C2 - 30742818
AN - SCOPUS:85064909262
VL - 107
SP - 1613
EP - 1620
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
SN - 0003-4975
IS - 6
ER -
