Transbronchial real-time lung tumor localization with folate receptor–targeted near-infrared molecular imaging: A proof of concept study in animal models

医学 纤维镜 叶酸受体 体内 病理 核医学 荧光寿命成像显微镜 离体 荧光 癌症 内科学 外科 光学 癌细胞 物理 生物技术 生物
作者
Tsukasa Ishiwata,Yoshihisa Hiraishi,Nicholas Bernards,Yuki Sata,Alexander Gregor,Masato Aragaki,Kazuhiro Yasufuku
出处
期刊:The Journal of Thoracic and Cardiovascular Surgery [American Association for Thoracic Surgery]
卷期号:165 (6): e240-e251 被引量:2
标识
DOI:10.1016/j.jtcvs.2022.09.042
摘要

The diagnostic yield of bronchoscopy is not satisfactory, even with recent navigation technologies, especially for tumors located outside of the bronchial lumen. Our objective was to perform a preclinical assessment of folate receptor-targeted near-infrared imaging-guided bronchoscopy to detect peribronchial tumors.Pafolacianine, a folate receptor-targeted molecular imaging agent, was used as a near-infrared fluorescent imaging agent. An ultra-thin composite optical fiberscope was used for laser irradiation and fluorescence imaging. Subcutaneous xenografts of KB cells in mice were used as folate receptor-positive tumors. Tumor-to-background ratio was calculated by the fluorescence intensity value of muscle tissues acquired by the ultra-thin composite optical fiberscope system and validated using a separate spectral imaging system. Ex vivo swine lungs into which pafolacianine-laden KB tumors were transplanted at various sites were used as a peribronchial tumor model.With the in vivo murine model, tumor-to-background ratio observed by ultra-thin composite optical fiberscope peaked at 24 hours after pafolacianine injection (tumor-to-background ratio: 2.56 at 0.05 mg/kg, 2.03 at 0.025 mg/kg). The fluorescence intensity ratios between KB tumors and normal mouse lung parenchyma postmortem were 6.09 at 0.05 mg/kg and 5.08 at 0.025 mg/kg. In the peribronchial tumor model, the ultra-thin composite optical fiberscope system could successfully detect fluorescence from pafolacianine-laden folate receptor-positive tumors with 0.05 mg/kg at the carina and those with 0.025 mg/kg and 0.05 mg/kg in the peripheral airway.Transbronchial detection of pafolacianine-laden folate receptor-positive tumors by near-infrared imaging was feasible in ex vivo swine lungs. Further in vivo preclinical assessment is needed to confirm the feasibility of this technology.
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