Nuutinen P J, Chatlani P T, Bedwell J, MacRobert A J, Phillips D, Bown S G
Department of Surgery, Rayne Institute, University College London, UK.
Br J Cancer. 1991 Dec;64(6):1108-15. doi: 10.1038/bjc.1991.473.
Necrosis of small volumes of tumour tissue with photodynamic therapy (PDT) can be achieved relatively easily. For this to be clinically relevant, it is essential to know what the same treatment parameters do to adjacent normal tissues into which the tumour has spread. For pancreatic cancers, local spread to vital structures is common. We have studied chemical extraction, microscopic fluorescence kinetics and photodynamic effects of disulphonated aluminum phthalocyanine (AlS2Pc) in normal pancreas and adjacent tissues in hamsters. Chemical extraction exhibited a peak duodenal concentration of AlS2Pc 48 h after sensitisation, with levels much higher than in stomach and pancreas. With microscopic fluorescence photometry highest levels were seen in duodenal submucosa and bile duct walls 48 h after photosensitisation. Pancreatic ducts, duodenal mucosa and gastric mucosa and submucosa exhibited intermediate fluorescence with relatively weak fluorescence in pancreatic acinar tissue and the muscle layer of the stomach. As expected, on the basis of fluorescence intensity and chemical extraction studies, the duodenal and bile duct wall were the most vulnerable tissues to photodynamic therapy. When the dose of 5 mumol kg-1 of sensitiser was used, duodenal perforations, gastric ulcers and transudation of bile from the bile duct occurred. However, the lesions in the stomach and bile duct healed without perforation or obstruction, so only the duodenum was at risk of serious, irreversible damage. Using a lower dose of photosensitiser markedly reduced damage.
通过光动力疗法(PDT)实现小体积肿瘤组织的坏死相对容易。要使其具有临床相关性,必须了解相同的治疗参数对肿瘤已扩散至的相邻正常组织会产生何种影响。对于胰腺癌而言,局部扩散至重要结构很常见。我们研究了二磺酸铝酞菁(AlS2Pc)在仓鼠正常胰腺及相邻组织中的化学提取、微观荧光动力学和光动力效应。化学提取显示,致敏后48小时十二指肠中AlS2Pc浓度达到峰值,其水平远高于胃和胰腺。通过微观荧光光度法,致敏后48小时在十二指肠黏膜下层和胆管壁观察到最高水平的荧光。胰管、十二指肠黏膜、胃黏膜及黏膜下层呈现中等荧光,胰腺腺泡组织和胃肌层荧光相对较弱。正如基于荧光强度和化学提取研究所预期的那样,十二指肠和胆管壁是光动力疗法最易受损的组织。当使用5 μmol kg-1的敏化剂剂量时,出现了十二指肠穿孔、胃溃疡以及胆管胆汁渗出。然而,胃和胆管的病变愈合且未发生穿孔或梗阻,因此只有十二指肠有遭受严重不可逆损伤的风险。使用较低剂量的光敏剂可显著减少损伤。