目的:胆管癌(CCA)的诊断准确性不足,有必要探索新的诊断方法。原卟啉IX(PpIX),5-氨基乙酰丙酸(5-ALA)的代谢产物,在蓝光曝光时发出红色荧光。因为它选择性地积累在癌细胞中,使用5-ALA(5-ALA-PDD)的光动力诊断已被纳入各种癌症类型的临床实践。然而,目前还没有能够捕获来自PpIX的荧光的装置,用于胆道内的实时5-ALA-PDD,很大程度上是由于设备小型化的挑战。
方法:为了研究实时5ALA-PDD在CCA中的可行性,我们开发了胆管镜检查系统的两个基本组件:小直径柔性相机和发射蓝光的光导.我们在实验凝胶和动物模型中使用这些设备评估了PpIX荧光的可检测性。
结果:我们的相机和光导被平滑地插入现有胆道镜的管腔中。在相机尖端结合长通滤光片可以有效检测红色荧光,而不会显着影响白光观察。这些装置的整合促进了来自含有浓度为5μM或更高的PpIX的凝胶的红色荧光的清晰可视化。此外,当观察用5-ALA治疗的裸鼠皮下人CCA肿瘤模型时,与肿瘤周围皮下区域相比,我们成功地证明了来自肿瘤中PpIX积累的明显的红色荧光.
结论:我们的设备组合的集成有望在人类CCA中实现实时5-ALA-PDD,有可能提高这种复杂情况的诊断准确性。
OBJECTIVE: The diagnostic accuracy for cholangiocarcinoma (CCA) is inadequate, necessitating the exploration of novel diagnostic approaches. Protoporphyrin IX (Pp IX), a metabolic product of 5-aminolevulinic acid (5-ALA), emits red fluorescence upon blue light exposure. Because it accumulates selectively in cancer cells, photodynamic diagnosis using 5-ALA (5-ALA-PDD) has been integrated into clinical practice for diverse cancer types. Nevertheless, there is currently no device capable of capturing Pp IX-derived fluorescence for real-time 5-ALA-PDD within the biliary tract, largely due to challenges in device miniaturization.
METHODS: To investigate the feasibility of real-time 5ALA-PDD in CCA, we developed two essential components of the cholangioscopy system: a small-diameter flexible camera and a light guide for emitting blue light. We evaluated the detectability of Pp IX fluorescence using these devices in experimental gels and animal models.
RESULTS: Our camera and light guide were smoothly inserted into the lumen of existing cholangioscopes. Incorporating a long-pass filter at the camera tip enabled efficient detection of red fluorescence without significantly impacting white-light observation. The integration of these devices facilitated clear visualization of red fluorescence from gels containing Pp IX at concentrations of 5 μM or higher. Additionally, when observing subcutaneous human CCA tumor models in nude mice treated with 5-ALA, we successfully demonstrated distinct red fluorescence from Pp IX accumulation in tumors compared to peritumoral subcutaneous areas.
CONCLUSIONS: The integration of our device combination holds promise for real-time 5-ALA-PDD in human CCA, potentially enhancing the diagnostic accuracy for this complex condition.