Ris H B, Altermatt H J, Stewart C M, Schaffner T, Wang Q, Lim C K, Bonnett R, Althaus U
Department of Thoracic and Cardiovascular Surgery, University of Bern, Switzerland.
Int J Cancer. 1993 Sep 9;55(2):245-9. doi: 10.1002/ijc.2910550213.
The therapeutic index of meta-tetrahydroxyphenylchlorin-mediated photodynamic therapy (mTHPC-PDT) was assessed in BALB/c nude mice bearing human malignant mesothelioma xenografts. Equal doses of 650 nm laser light were delivered to the tumour and to an equal-sized area of the hind leg (control site) after i.p. administration of mTHPC. Twenty-one groups of 6 animals each were treated under various drug-light conditions and at drug-light intervals ranging from 4 hr to 6 days. After light delivery the extent of tumour necrosis and the depth of alterations in normal tissue were assessed by light microscopy of standardized histological sections. A therapeutic index (TI) of mTHPC-PDT was defined as the cross-sectional area of tumour necrosis per depth of visible tissue injury at the control site. This TI was strongly related to the conditions of treatment. In particular, it was increased by prolonging the drug-light interval up to 5 days and by increasing the dose of light for any dose of drug. The most profound increase of TI was obtained by increasing the intensity of light administered at the chosen interval while reducing the dose of drug. Our findings suggest that threshold conditions operate in PDT and have important implications for clinical application of the treatment.
在携带人恶性间皮瘤异种移植瘤的BALB/c裸鼠中评估了间四羟基苯基二氢卟吩介导的光动力疗法（mTHPC-PDT）的治疗指数。腹腔注射mTHPC后，将等量的650 nm激光照射到肿瘤以及后肢的同等大小区域（对照部位）。21组，每组6只动物，在不同的药物-光照条件下以及4小时至6天的药物-光照间隔下进行治疗。光照后，通过标准化组织学切片的光学显微镜评估肿瘤坏死程度和正常组织的改变深度。mTHPC-PDT的治疗指数（TI）定义为对照部位可见组织损伤深度下肿瘤坏死的横截面积。该TI与治疗条件密切相关。特别是，通过将药物-光照间隔延长至5天以及对任何药物剂量增加光照剂量，TI会增加。通过在选定间隔增加光照强度同时减少药物剂量，可使TI得到最显著的增加。我们的研究结果表明，阈值条件在光动力疗法中起作用，并且对该治疗方法的临床应用具有重要意义。
