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A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model

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Title: A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model
Authors: Ishiwata, Tsukasa Browse this author
Seki, Takeshi Browse this author
Gregor, Alexander Browse this author
Aragaki, Masato Browse this author
Motooka, Yamato Browse this author
Kinoshita, Tomonari Browse this author
Inage, Terunaga Browse this author
Bernards, Nicholas Browse this author
Ujiie, Hideki Browse this author
Chen, Zhenchian Browse this author
Effat, Andrew Browse this author
Chen, Juan Browse this author
Zheng, Gang Browse this author
Tatsumi, Koichiro Browse this author
Yasufuku, Kazuhiro Browse this author
Keywords: Fluorescence imaging
lung cancer
orthotopic lung cancer mouse model
Issue Date: Jan-2021
Publisher: AME Publishing Company
Journal Title: Translational Lung Cancer Research
Volume: 10
Issue: 1
Start Page: 243
End Page: 251
Publisher DOI: 10.21037/tlcr-20-813
Abstract: Background: Establishing the efficacy of novel photosensitizers (PSs) for phototherapy of lung cancer requires in vivo study prior to clinical evaluation. However, previously described animal models are not ideal for assessing transbronchial approaches with such PSs. Methods: An ultra-small parallel-type composite optical fiberscope (COF) with a 0.97 mm outer diameter tip. The integration of illumination and laser irradiation fibers inside the COF allows simultaneous white-light and fluorescence imaging, as well as real-time monitoring of tip position during laser phototherapy. An orthotopic lung cancer mouse model was created with three human lung cancer cell lines transbronchially inoculated into athymic nude mice. The COF was inserted transbronchially into a total of 15 mice for tumor observation. For in vivo fluorescence imaging, an organic nanoparticle, porphysome, was used as a PS. Laser excitation through the COF was performed at 50 mW using a 671 nm source. Results: The overall success rate for creating orthotopic lung tumors was 71%. Transbronchial white light images were successfully captured by COF. Access to the left main bronchus was successful in 87% of mice (13/15), the right main bronchus to the cranial lobe bronchus level in 100% (15/15), and to the right basal trifurcation of the middle lobe, caudal lobe and accessory lobe in 93% (14/15). For transbronchial tumor localization of orthotopic lung cancer tumors, PS-laden tumor with the strong signal was clearly contrasted from the normal bronchial wall. Conclusions: The ultra-small COF enabled reliable transbronchial access to orthotopic human lung cancer xenografts in vivo. This method could serve as a versatile preclinical research platform for PS evaluation in lung cancer, enabling transbronchial approaches in in vivo survival models inoculated with human lung cancer cells.
Type: article
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 氏家 秀樹

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