Andrejevic Blant S, Ballini J P, van den Bergh H, Fontolliet C, Wagnières G, Monnier P
Institute of Pathology, University of Lausanne, Switzerland.
Photochem Photobiol. 2000 Mar;71(3):333-40. doi: 10.1562/0031-8655(2000)071<0333:TDBOTM>2.0.CO;2.
The pharmacokinetics of the photosensitizer used play a key role in the understanding of the mechanism of photodynamic therapy-induced damage. Fluorescence microscopy was used to compare time-dependent biodistribution of tetra(m-hydroxyphenyl)chlorin (mTHPC) and benzoporphyrin derivative monoacid ring A (BPD-MA) in different hamster tissues, including an early, chemically induced, squamous cell carcinoma. Following injection of 0.5 mg/kg body weight of mTHPC and 2.0 mg/kg BPD-MA, groups of three animals were sacrificed at different time points and a series of fluorescence micrographs from different excised organs were analyzed. The highest fluorescence intensities of mTHPC were observed at 96 h for squamous epithelia and skin and at 48 h for smooth muscle. There is no real peak of BPD-MA fluorescence between 30 min and 3 h in the basal epithelial layers, fibroconnective tissue, muscles or blood vessels. At 4 h after injection, the fluorescence level of BPD-MA decreased and at 24 h it had returned to background level in all observed tissues. The significantly faster clearance of BPD-MA is the principal advantage as compared to mTHPC. However, similar localization patterns in different tissues with essentially vascular affinity represent a possible disadvantage for treating early malignancies with BPD-MA as compared to mTHPC, which is mainly localized in various epithelia. For both photosensitizers no significant selectivity between early squamous cell carcinoma and healthy mucosae is seen. Pharmacokinetic studies of different photosensitizers in an appropriate animal model are essential for selecting new-generation photosensitizers with the most favorable localization for photodynamic therapy of early malignancies in hollow organs.
所使用的光敏剂的药代动力学在理解光动力疗法诱导损伤的机制中起着关键作用。采用荧光显微镜比较了四（间羟基苯基）氯卟啉（mTHPC）和苯并卟啉衍生物单酸环A（BPD-MA）在不同仓鼠组织中的时间依赖性生物分布，包括早期化学诱导的鳞状细胞癌。分别注射0.5mg/kg体重的mTHPC和2.0mg/kg的BPD-MA后，在不同时间点处死每组三只动物，并分析从不同切除器官获得的一系列荧光显微照片。mTHPC在鳞状上皮和皮肤中96小时时荧光强度最高，在平滑肌中48小时时荧光强度最高。在基底上皮层、纤维结缔组织、肌肉或血管中，BPD-MA在30分钟至3小时之间没有真正的荧光峰值。注射后4小时，BPD-MA的荧光水平下降，24小时时在所有观察到的组织中已恢复到背景水平。与mTHPC相比，BPD-MA清除速度明显更快是其主要优势。然而，与主要定位于各种上皮的mTHPC相比，BPD-MA在不同组织中具有基本血管亲和力的类似定位模式可能是治疗早期恶性肿瘤的一个劣势。对于这两种光敏剂，早期鳞状细胞癌和健康黏膜之间均未观察到明显的选择性。在合适的动物模型中对不同光敏剂进行药代动力学研究对于选择新一代光敏剂至关重要，这些光敏剂在中空器官早期恶性肿瘤的光动力治疗中具有最有利的定位。
