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

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...

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Autores principales: Ishiwata, Tsukasa, Seki, Takeshi, Gregor, Alexander, Aragaki, Masato, Motooka, Yamato, Kinoshita, Tomonari, Inage, Terunaga, Bernards, Nicholas, Ujiie, Hideki, Chen, Zhenchian, Effat, Andrew, Chen, Juan, Zheng, Gang, Tatsumi, Koichiro, Yasufuku, Kazuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867757/
https://www.ncbi.nlm.nih.gov/pubmed/33569308
http://dx.doi.org/10.21037/tlcr-20-813
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author Ishiwata, Tsukasa
Seki, Takeshi
Gregor, Alexander
Aragaki, Masato
Motooka, Yamato
Kinoshita, Tomonari
Inage, Terunaga
Bernards, Nicholas
Ujiie, Hideki
Chen, Zhenchian
Effat, Andrew
Chen, Juan
Zheng, Gang
Tatsumi, Koichiro
Yasufuku, Kazuhiro
author_facet Ishiwata, Tsukasa
Seki, Takeshi
Gregor, Alexander
Aragaki, Masato
Motooka, Yamato
Kinoshita, Tomonari
Inage, Terunaga
Bernards, Nicholas
Ujiie, Hideki
Chen, Zhenchian
Effat, Andrew
Chen, Juan
Zheng, Gang
Tatsumi, Koichiro
Yasufuku, Kazuhiro
author_sort Ishiwata, Tsukasa
collection PubMed
description 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.
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spelling pubmed-78677572021-02-09 A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model Ishiwata, Tsukasa Seki, Takeshi Gregor, Alexander Aragaki, Masato Motooka, Yamato Kinoshita, Tomonari Inage, Terunaga Bernards, Nicholas Ujiie, Hideki Chen, Zhenchian Effat, Andrew Chen, Juan Zheng, Gang Tatsumi, Koichiro Yasufuku, Kazuhiro Transl Lung Cancer Res Original Article 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. AME Publishing Company 2021-01 /pmc/articles/PMC7867757/ /pubmed/33569308 http://dx.doi.org/10.21037/tlcr-20-813 Text en 2021 Translational Lung Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Ishiwata, Tsukasa
Seki, Takeshi
Gregor, Alexander
Aragaki, Masato
Motooka, Yamato
Kinoshita, Tomonari
Inage, Terunaga
Bernards, Nicholas
Ujiie, Hideki
Chen, Zhenchian
Effat, Andrew
Chen, Juan
Zheng, Gang
Tatsumi, Koichiro
Yasufuku, Kazuhiro
A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model
title A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model
title_full A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model
title_fullStr A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model
title_full_unstemmed A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model
title_short A preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model
title_sort preclinical research platform to evaluate photosensitizers for transbronchial localization and phototherapy of lung cancer using an orthotopic mouse model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867757/
https://www.ncbi.nlm.nih.gov/pubmed/33569308
http://dx.doi.org/10.21037/tlcr-20-813
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