Photodynamic therapy using verteporfin photosensitization in the pancreas and surrounding tissues in the Syrian golden hamster
Photodynamic therapy using verteporfin photosensitization in the pancreas and surrounding tissues in the Syrian golden hamster
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DOI：
10.1159/000101874
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发表时间：
2007-01-01
期刊：
影响因子：
3.6
通讯作者：
Pereira, Stephen P.
中科院分区：
文献类型：
--
作者：
Ayaru, Lakshmana;Wittmann, Johannes;Pereira, Stephen P.
背景/目的：光动力疗法（PDT）是局部晚期胰腺癌的一种潜在治疗方法。我们的目的是评估使用维替泊芬（苯并卟啉衍生物单酸A -一种新型光敏剂，具有短的药物-光间隔和有限的皮肤光敏性）在叙利亚金黄地鼠中进行间质PDT的安全性，并将其与我们先前在临床前和临床研究中评估的meso-四羟基苯基二氢卟酚（mTHPC）进行比较。研究方法：在剖腹手术时通过下腔静脉注射给予维替泊芬（2 mg/kg）（n = 57），在5、15、30、60和240 min以及24 h定量血浆水平。光敏化后15分钟，用690 nm红色激光（150 mW）照射组织（肝脏、胰腺、十二指肠、结肠、主动脉），光剂量范围为1 - 100 J/cm（2）。PDT对靶器官和邻近结构的影响在死后第3天和第21天或死亡时进行评估。结果：维替泊芬的消除半衰期为4 ~ 5 h。10、25和50 J/cm（2）的光剂量分别在仓鼠胰腺、肝脏和结肠中是安全的，并产生直径为3（范围3 - 4）、10（9 - 10）和7（7 - 8）mm的凝固性坏死病变。胶原蛋白对损伤具有抵抗力，损伤主要通过正常组织的再生而愈合。在较高的光剂量下，坏死延伸到器官边缘，有时会导致密封的十二指肠穿孔，如mTHPC所示。总结：维替泊芬的安全性特征与mTHPC非常相似，优点是药物-光间隔和药物消除时间更短。在胰腺癌中使用这种光敏剂的I期临床研究应该是可行的。版权所有（c）2007 S. Karger AG、巴塞尔和IAP。
Background/Aim: Photodynamic therapy (PDT) is a potential treatment for locally advanced pancreatic cancer. We aimed to assess the safety of interstitial PDT using verteporfin ( benzoporphyrin derivative monoacid A - a novel photosensitizer with a short drug-light interval and limited cutaneous photosensitivity) in the Syrian golden hamster, and compare it to meso-tetrahydroxyphenylchlorin ( mTHPC) which we have previously evaluated in preclinical and clinical studies. Methods: Verteporfin ( 2 mg/kg) was administered at laparotomy by inferior vena caval injection (n = 57), with plasma levels quantified at 5, 15, 30, 60 and 240 min, and 24 h. 15 min after photosensitization, tissues ( liver, pancreas, duodenum, colon, aorta) were illuminated with 690 nm red laser light ( 150 mW), at a range of light doses ( 1 - 100 J/cm(2)). The PDT effects on the targeted organ and adjacent structures were assessed at post-mortem on days 3 and 21, or at the time of death. Results: The elimination half-life of verteporfin was 4 - 5 h. Light doses of 10, 25 and 50 J/cm(2) were safe in the hamster pancreas, liver and colon, respectively, and produced coagulative necrotic lesions of 3 ( range 3 - 4), 10 ( 9 - 10) and 7 ( 7 - 8) mm diameter. Collagen was resistant to damage and lesions healed mainly by regeneration of normal tissue. At higher light doses, necrosis extended to the edge of organs, sometimes causing sealed duodenal perforations as seen with mTHPC. Conclusion: The safety profile of verteporfin is very similar to mTHPC, with the advantages of a shorter drug-light interval and drug elimination time. Phase I clinical studies using this photosensitizer in pancreatic cancer should be feasible. Copyright (c) 2007 S. Karger AG, Basel and IAP.