Photodynamic therapy of early squamous cell carcinoma with tetra(m-hydroxyphenyl)chlorin: optimal drug-light interval
Photodynamic therapy of early squamous cell carcinoma with tetra(m-hydroxyphenyl)chlorin: optimal drug-light interval
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DOI：
10.1038/bjc.1997.502
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发表时间：
1997-10-01
影响因子：
8.8
通讯作者：
Monnier, P
中科院分区：
文献类型：
--
作者：
AndrejevicBlant, S;Hadjur, C;Monnier, P
采用四（间羟基苯基）氯（mTHPC）通过两种互补方式：照射试验和离体荧光显微镜评估早期鳞状细胞癌有效光动力治疗（PDT）的最佳药物-光间隔。实验采用叙利亚仓鼠颊袋肿瘤模型。对荷瘤和对侧健康颊袋粘膜分别在650 nm和514 nm处进行光动力治疗。在注射0.5 mg kg（-1）体重的mTHPC后6小时至12天内，分别以150 mW cm（-2）的光剂量率和100 mW cm（-2）的光剂量分别给予12 J cm（-2）和80 J cm（-2）的光剂量。观察到两种组织学上不同类型的组织损伤：第一，注射染料后48小时内发生PDT的病例为非选择性和非特异性缺血性血管坏死；第二，注射染料后超过72小时发生PDT的组织特异性PDT损伤为凝固性坏死。荧光显微镜观察的mTHPC的时间依赖性生物分布显示，早期SCC与健康粘膜的相对荧光强度差异微弱且不显著。注射后2天，药物主要局限于血管内皮细胞。在此之后，染料在鳞状上皮中积聚，浓度在第4天达到峰值。在所有时间点，在固有层和横纹肌下观察到弱荧光强度。从这些研究中获得的信息很可能与临床试验相关，因为它表明静脉注射后4至8天之间的时间延迟对于中空器官早期恶性肿瘤的PDT来说是最佳的。
The optimal drug-light interval for effective photodynamic therapy (PDT) of early squamous cell carcinomas was evaluated with tetra(m-hydroxyphenyl)chlorin (mTHPC) by means of two complementary modalities: irradiation tests and ex vivo fluorescence microscopy. A Syrian hamster cheek pouch tumour model was used in these experiments. Photodynamic therapy on both tumour-bearing and contralateral healthy cheek pouch mucosae was performed at 650 nm and 514 nm. Light doses of 12 J cm(-2) were delivered at a light dose rate of 150 mW cm(-2) and light doses of 80 J cm(-2) were delivered at a light dose rate of 100 mW cm(-2) respectively, al these two wavelengths, between 6 h and 12 days after the injection of 0.5 mg kg(-1) body weight mTHPC. Two histologically different types of tissue damage were observed: first, a non-selective and non-specific ischaemic Vascular necrosis for the cases in which PDT took place during the first 48 h after the injection of the dye and, second, tissue-specific PDT damage, as a coagulation necrosis, when PDT took place more than 72 h after injection of the dye. The time-dependent biodistribution of mTHPC investigated by fluorescence microscopy shows a weak and non-significant difference in relative fluorescence intensities between early SCC and healthy mucosae. Up to 2 days after the injection, the drug is mainly localized in the endothelial cells of the blood vessels. After this period, the dye accumulates in the squamous epithelia with a concentration peaking at 4 days. At all time points, a weak fluorescence intensity is observed in the underlying lamina propria and striated muscle. The information obtained from these studies could well be relevant to clinical trials as it suggests that time delays between 4 and 8 days after i.v. injection should be optimal for PDT of early malignancies in hollow organs.