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
Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Transl Lung Cancer Res. 2021 Jan;10(1):243-251. doi: 10.21037/tlcr-20-813.
Establishing the efficacy of novel photosensitizers (PSs) for phototherapy of lung cancer requires study prior to clinical evaluation. However, previously described animal models are not ideal for assessing transbronchial approaches with such PSs.
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 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.
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.
The ultra-small COF enabled reliable transbronchial access to orthotopic human lung cancer xenografts . This method could serve as a versatile preclinical research platform for PS evaluation in lung cancer, enabling transbronchial approaches in survival models inoculated with human lung cancer cells.
在进行临床评估之前，需要对新型光敏剂（PSs）用于肺癌光疗的疗效进行研究。然而，先前描述的动物模型并不适合评估使用此类PSs的经支气管治疗方法。
一种外径为0.97 mm的超小型平行型复合光纤镜（COF）。COF内部集成了照明光纤和激光照射光纤，可实现白光和荧光成像同步，以及激光光疗期间对尖端位置的实时监测。通过经支气管将三种人肺癌细胞系接种到无胸腺裸鼠体内，建立原位肺癌小鼠模型。将COF经支气管插入总共15只小鼠体内进行肿瘤观察。对于荧光成像，使用有机纳米颗粒卟啉体作为PS。使用671 nm光源，通过COF以50 mW进行激光激发。
原位肺肿瘤的总体成功率为71%。COF成功捕获了经支气管白光图像。87%（13/15）的小鼠成功进入左主支气管，100%（15/15）的小鼠成功进入右主支气管至颅叶支气管水平，93%（14/15）的小鼠成功进入中叶、尾叶和副叶的右基底三叉处。对于原位肺癌肿瘤的经支气管肿瘤定位，载有PS的肿瘤信号强，与正常支气管壁形成明显对比。
超小型COF能够可靠地经支气管进入原位人肺癌异种移植瘤。该方法可作为一个通用的临床前研究平台，用于肺癌中PS的评估，能够在接种人肺癌细胞的生存模型中采用经支气管治疗方法。
