Andrejevic-Blant S, Hadjur C, Ballini J P, Wagnières G, Fontolliet C, van den Bergh H, Monnier P
Department of Otolaryngology, Head and Neck Surgery-CHUV Hospital, Lausanne, Switzerland.
Br J Cancer. 1997;76(8):1021-8. doi: 10.1038/bjc.1997.502.
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.
采用四（间羟基苯基）氯卟啉（mTHPC），通过两种互补方式（照射试验和离体荧光显微镜检查）评估早期鳞状细胞癌有效光动力疗法（PDT）的最佳药物 - 光间隔。这些实验使用叙利亚仓鼠颊囊肿瘤模型。在650 nm和514 nm对荷瘤及对侧健康颊囊黏膜进行光动力疗法。在注射0.5 mg kg⁻¹体重的mTHPC后6小时至12天之间，在这两个波长下，分别以150 mW cm⁻²的光剂量率给予12 J cm⁻²的光剂量，以及以100 mW cm⁻²的光剂量率给予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，在注射染料后的头48小时内进行PDT的情况下，出现非选择性和非特异性缺血性血管坏死；第二，在注射染料后超过72小时进行PDT时，出现组织特异性PDT损伤，表现为凝固性坏死。通过荧光显微镜检查研究的mTHPC的时间依赖性生物分布显示，早期鳞状细胞癌和健康黏膜之间的相对荧光强度存在微弱且无统计学意义的差异。注射后长达2天，药物主要定位在血管内皮细胞中。在此之后，染料在鳞状上皮中积累，浓度在4天时达到峰值。在所有时间点，在下方的固有层和横纹肌中观察到微弱的荧光强度。从这些研究中获得的信息很可能与临床试验相关，因为它表明静脉注射后4至8天的时间延迟对于中空器官早期恶性肿瘤的PDT应该是最佳的。
