Ris H B, Im Hof V, Stewart C M, Mettler D, Altermatt H J
Department of Thoracic and Cardiovascular Surgery, University of Berne, Switzerland.
Lasers Surg Med. 1998;23(1):25-32. doi: 10.1002/(sici)1096-9101(1998)23:1<25::aid-lsm4>3.0.co;2-y.
Photodynamic therapy (PDT) with mTHPC and polyethylene glycol-derived mTHPC (pegylated mTHPC) was compared on nude mice bearing human squamous cell carcinoma and adenocarcinoma xenografts. The same treatment regimens were applied to the bronchi of tumor-free minipigs to assess injury to normal tissue.
STUDY DESIGN/MATERIALS AND METHODS: Laser light (652 nm, 20 J/cm2) was delivered as surface radiation to the xenografts 4 days after intraperitoneal administration of 0.1 mg/kg mTHPC or an equimolar dose of pegylated mTHPC, respectively. The extent of tumor necrosis was assessed by histomorphometry. Endobronchial PDT was performed on the bronchi of minipigs with the same drug and light doses at drug-light intervals ranging from 12-96 hr.
Both sensitizers produced larger necrosis of squamous cell carcinoma and adenocarcinoma xenografts than was observed in untreated controls (P < 0.005). Pegylated mTHPC led to larger tumor necrosis than mTHPC in squamous cell carcinoma (P < 0.001), but not in adenocarcinoma xenografts. mTHPC-PDT resulted in ulceration and necrosis of bronchial mucosa in minipigs at drug-light intervals ranging from 12-48 hr, which was not observed after use of pegylated mTHPC.
In this setting, pegylated mTHPC had advantages as a photosensitiser compared to mTHPC.
在携带人鳞状细胞癌和腺癌异种移植瘤的裸鼠身上,比较了用间四(羟基苯基)氯代卟啉(mTHPC)和聚乙二醇化间四(羟基苯基)氯代卟啉(聚乙二醇化mTHPC)进行的光动力疗法(PDT)。将相同的治疗方案应用于无肿瘤小型猪的支气管,以评估对正常组织的损伤。
研究设计/材料与方法:分别在腹腔注射0.1mg/kg mTHPC或等摩尔剂量的聚乙二醇化mTHPC 4天后,以表面辐射的方式将激光(652nm,20J/cm²)照射到异种移植瘤上。通过组织形态计量学评估肿瘤坏死程度。在小型猪的支气管上进行支气管内PDT,使用相同的药物和光剂量,药物-光间隔时间为12 - 96小时。
与未治疗的对照组相比,两种光敏剂都使鳞状细胞癌和腺癌异种移植瘤产生了更大程度的坏死(P < 0.005)。在鳞状细胞癌中,聚乙二醇化mTHPC导致的肿瘤坏死比mTHPC更大(P < 0.001),但在腺癌异种移植瘤中并非如此。mTHPC - PDT在药物 - 光间隔时间为12 - 48小时时导致小型猪支气管黏膜溃疡和坏死,而使用聚乙二醇化mTHPC后未观察到这种情况。
在这种情况下,与mTHPC相比,聚乙二醇化mTHPC作为光敏剂具有优势。