Mlkvy P, Messmann H, Pauer M, Stewart J C, Millson C E, MacRobert A J, Bown S G
National Cancer Centre, Bratislava, Slovakia.
Br J Cancer. 1996 Jun;73(12):1473-9. doi: 10.1038/bjc.1996.279.
Photodynamic therapy (PDT) has the potential to destroy small tumours with safe healing of adjacent normal tissue. This study looks at the effects of PDT on the normal pancreas and adjacent tissues in hamsters using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC). Pharmacokinetic studies used fluorescence microscopy on sections of pancreas, stomach and duodenum 1 h to 6 days after mTHPC. Highest levels of sensitiser were seen in the gastric and duodenal mucosa and in the acinar pancreas after 2-4 days. For PDT, light at 652 nm was delivered by placing a 0.2 mm diameter bare-ended fibre against the tissue. An energy of 50 J was used 2 or 4 days after 0.1 or 0.3 mg kg-1 mTHPC and animals killed 1 to 7 days later. Maximum necrosis was seen 3 days after PDT with lesions up to 4 mm in pancreas, 4.5 mm in duodenum and 2.5 mm in stomach. By fractionating the light dose, the lesion size could be increased by 30%. The main complication was free or sealed duodenal perforation (avoided by shielding the duodenum). Partial, reversible bile duct obstruction was seen occasionally. There was no macroscopic damage to the bile ducts or major blood vessels. Apart from the duodenum, all lesions healed safely. In this animal model, only the duodenum was at risk of serious, irreversible damage. Treatment is likely to be safer in the much thicker human duodenum. mTHPC is a powerful photosensitiser and suitable for further study for tumours in the region of the pancreas although care is required near the duodenum.
光动力疗法(PDT)有潜力破坏小肿瘤,同时使相邻正常组织安全愈合。本研究观察了使用光敏剂中-四羟基苯基氯卟啉(mTHPC)的光动力疗法对仓鼠正常胰腺及相邻组织的影响。药代动力学研究在给予mTHPC后1小时至6天,对胰腺、胃和十二指肠切片进行荧光显微镜检查。2 - 4天后,在胃和十二指肠黏膜以及腺泡胰腺中观察到最高水平的光敏剂。对于光动力疗法,通过将直径0.2毫米的裸端光纤置于组织上,输送652纳米的光。在给予0.1或0.3毫克/千克mTHPC后2或4天,使用50焦耳的能量,1至7天后处死动物。光动力疗法后3天可见最大坏死,胰腺病变达4毫米,十二指肠病变达4.5毫米,胃病变达2.5毫米。通过分次给予光剂量,病变大小可增加30%。主要并发症是十二指肠游离穿孔或封闭穿孔(通过屏蔽十二指肠可避免)。偶尔可见部分、可逆的胆管梗阻。胆管或主要血管无肉眼可见的损伤。除十二指肠外,所有病变均安全愈合。在这个动物模型中,只有十二指肠有发生严重、不可逆损伤的风险。在人类更厚的十二指肠中,治疗可能更安全。mTHPC是一种强大的光敏剂,适合进一步研究胰腺区域的肿瘤,不过在十二指肠附近需要谨慎操作。