Ris H B, Krueger T, Giger A, Lim C K, Stewart J C, Althaus U, Altermatt H J
Department of Thoracic and Cardiovascular Surgery, University of Berne, Switzerland.
Br J Cancer. 1999 Mar;79(7-8):1061-6. doi: 10.1038/sj.bjc.6690170.
The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.
在携带人恶性间皮瘤、鳞状细胞癌和腺癌异种移植瘤的裸鼠中，比较了间四羟基苯基二氢卟吩（mTHPC）和聚乙二醇衍生化的mTHPC（聚乙二醇化mTHPC）的光敏特性。在分别腹腔注射0.1 mg/kg体重的mTHPC和等摩尔剂量的聚乙二醇化mTHPC后，将652 nm的激光（20 J/cm²）照射到肿瘤（表面辐照度）以及动物后腿的同等大小区域。通过组织学评估肿瘤坏死程度和正常组织损伤情况。mTHPC和聚乙二醇化mTHPC在1 - 4天的药物 - 光照间隔下均可催化间皮瘤异种移植瘤中的光敏坏死。聚乙二醇化mTHPC的作用起效似乎较慢，但在第3天和第4天显著超过mTHPC，在第4天差异最为明显。在第4天，聚乙二醇化mTHPC在鳞状细胞异种移植瘤中诱导的光坏死也明显大于mTHPC，但在腺癌中并非如此，mTHPC在腺癌中显示出最大活性。聚乙二醇化mTHPC诱导的坏死程度在所有三种异种移植瘤中相同。mTHPC在1天的药物 - 光照间隔下导致皮肤和深层肌肉坏死，但在2 - 4天的药物 - 光照间隔下仅引起轻微的组织学变化。相比之下，在任何评估的药物 - 光照间隔下，在相同治疗条件下，聚乙二醇化mTHPC在正常组织中未导致组织学可检测到的变化。在本研究中，与mTHPC相比，聚乙二醇化mTHPC作为光敏剂具有优势。给药4天后，通过高效液相色谱法在未照射的动物中测量mTHPC和聚乙二醇化mTHPC的组织浓度。在间皮瘤、腺癌和鳞状细胞癌异种移植瘤中，两种敏化剂的肿瘤摄取没有显著差异。在该模型中，组织浓度测量对于预测光敏作用的用途有限。
