Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model
Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model
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DOI：
10.3171/jns.2006.104.1.109
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发表时间：
2006-01-01
影响因子：
4.1
通讯作者：
Hirschberg, H
中科院分区：
文献类型：
--
作者：
Angell-Petersen, E;Spetalen, S;Hirschberg, H
目的。高级别胶质瘤治疗失败通常是由于切除部位的局部复发，这表明更积极的局部治疗可能是有益的。光动力疗法 (PDT) 是一种局部治疗方法，涉及使用肿瘤定位光敏药物，在本例中为氨基乙酰丙酸 (ALA)。该效果取决于传递到目标组织的总光能，但也可能受到光传递速率的影响。方法。体外实验表明，BT4C多细胞肿瘤球体对ALA PDT的敏感性取决于光传输速率（注量率）。 BT4C 肿瘤在 BD-IX 大鼠颅内建立。冷冻组织切片的显微荧光测定表明，注射 ALA 后，产生的光敏作用具有优于 200:1 的肿瘤/正常组织选择性。腹膜内 ALA 注射 (125 mg/kg) 4 小时后，26 J 的 632 nm 光在 15 分钟（高注量率）或 90 分钟（低注量率）内传递至间质。肿瘤诱导后14天治疗的动物的组织学检查表明，低注量率PDT后出现广泛的肿瘤坏死，但高注量率治疗后几乎没有任何坏死。 PDT 增加了肿瘤组织中的中性粒细胞浸润，但两种治疗方案相似。与未治疗的对照动物相比，在肿瘤诱导9天后施用低注量率PDT导致治疗大鼠的存活率具有统计学意义的显着延长。结论。仅当光以低速率传递时，ALA PDT 治疗才会引起肿瘤明显坏死。该治疗延长了荷瘤动物的生存期。
Object. Failure of treatment for high-grade gliomas is usually due to local recurrence at the site of resection, indicating that a more aggressive local therapy could be beneficial. Photodynamic therapy (PDT) is a local treatment involving the administration of a tumor-localizing photosensitizing drug, in this case aminolevulinic acid (ALA). The effect depends on the total light energy delivered to the target tissue, but may also be influenced by the rate Of light delivery.Methods. In vitro experiments showed that the sensitivity to ALA PDT of BT4C multicellular tumor spheroids depended oil the rate of light delivery (fluence rate). The BT4C tumors were established intracranially in BD-IX rats. Microfluorometry of frozen tissue Sections showed that photosensitization is produced with better than 200:1 tumor/normal tissue Selectivity after ALA injection. Four hours after intraperitoneal ALA injection (125 mg/kg), 26 J of 632 nm light was delivered interstitially over 15 (high fluence rate) or 90 (low fluence rate) Minutes. Histological examination of animals treated 14 days after tumor induction demonstrated extensive tumor necrosis after low-fluence-rate PDT, but hardly any necrosis after high-fluence-rate treatment. Neutrophil infiltration in tumor tissue was increased by PDT, but was similar for both treatment regimens. Low-fluence-rate PDT administered 9 days after tumor induction resulted in statistically significant prolongation Of survival for treated rats compared with nontreated control animals.Conclusions. Treatment with ALA PDT induced pronounced necrosis in tumors only if the light was delivered at a low rate. The treatment prolonged the Survival for tumor-bearing animals.