Transbronchial real-time lung tumor localization with folate receptor-targeted near-infrared molecular imaging: A proof of concept study in animal models
Transbronchial real-time lung tumor localization with folate receptor-targeted near-infrared molecular imaging: A proof of concept study in animal models
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DOI：
10.1016/j.jtcvs.2022.09.042
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发表时间：
2023-05-10
影响因子：
6
通讯作者：
Yasufuku，Kazuhiro
中科院分区：
文献类型：
--
作者：
Ishiwata，Tsukasa;Hiraishi，Yoshihisa;Yasufuku，Kazuhiro
支气管镜的诊断率并不令人满意，即使使用最新的导航技术，特别是对于位于支气管腔外的肿瘤。我们的目的是进行临床前评估叶酸受体为靶向的近红外成像引导支气管镜检查，以检测支气管周围tumors.MethodsPafolacianine，叶酸受体为靶向的分子成像剂，被用作近红外荧光成像剂。一种超薄复合光纤镜用于激光照射和荧光成像。将小鼠中KB细胞的皮下异种移植物用作叶酸受体阳性肿瘤。通过超薄复合光纤镜系统采集的肌肉组织的荧光强度值计算肿瘤与背景的比值，并使用单独的光谱成像系统进行验证。离体猪肺pafolacianine装载KB肿瘤移植在各个网站被用作支气管周围肿瘤model.ResultsWith在体内小鼠模型，超薄复合光纤观察到的肿瘤背景比在pafolacianine注射后24小时达到峰值（肿瘤背景比：2.56在0.05 mg/kg，2.03在0.025 mg/kg）。KB肿瘤和正常小鼠死后肺实质之间的荧光强度比在0.05 mg/kg和0.025 mg/kg时分别为6.09和5.08。在支气管周围肿瘤模型中，超薄复合光纤镜系统可以成功地检测到荧光从pafolacianine负载叶酸受体阳性肿瘤与0.05 mg/kg的隆突和那些与0.025 mg/kg和0.05 mg/kg的外周airway.ConclusionsTransbronchial检测pafolacianine负载叶酸受体阳性肿瘤的近红外成像是可行的，在离体猪肺。需要进一步的体内临床前评估来确认该技术的可行性。
ObjectiveThe 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.MethodsPafolacianine, 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.ResultsWith 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.ConclusionsTransbronchial 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.