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Photodynamic therapy of early squamous cell carcinoma with tetra(m-hydroxyphenyl)chlorin: optimal drug-light interval.

机译:四(间-羟基苯基)二氢卟酚对早期鳞状细胞癌的光动力治疗:最佳药物光间隔。

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摘要

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, at 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.
机译:通过两种互补方式,用四(间羟基苯基)二氢卟酚(mTHPC)评估了早期鳞状细胞癌有效光动力疗法(PDT)的最佳药物光间隔,方法是照射试验和离体荧光显微镜检查。在这些实验中使用了叙利亚仓鼠脸颊袋肿瘤模型。对荷瘤和对侧健康颊袋粘膜的光动力治疗分别在650 nm和514 nm进行。以150 mW cm(-2)的光剂量率传输12 J cm(-2)的光剂量,以100 mW cm(-2)的光剂量率传输80 J cm(-2)的光剂量)分别在注射0.5 mg kg(-1)体重的mTHPC后的6小时至12天之间的这两个波长处。观察到两种组织学上不同的组织损伤类型:首先是非选择性和非特异性缺血性血管坏死,这种情况是在染料注射后的第一个48小时内发生了PDT,第二种是组织特异性PDT染料注入后72小时以上发生PDT时,由于凝血坏死而引起的损害。荧光显微镜研究的mTHPC随时间变化的生物分布表明,早期SCC和健康黏膜之间的相对荧光强度存在弱弱且不显着的差异。注射后最多2天,药物主要位于血管内皮细胞中。在这段时间之后,染料在鳞状上皮中积累,浓度在4天达到峰值。在所有时间点,在固有的固有层和横纹肌中均观察到弱的荧光强度。从这些研究中获得的信息很可能与临床试验有关,因为它表明静脉注射后4到8天之间的时间延迟。对于中空器官的早期恶性肿瘤,PDT应该是最佳选择。

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