Photodynamic therapy of intracranial tissues: A preclinical comparative study of four different photosensitizers
Photodynamic therapy of intracranial tissues: A preclinical comparative study of four different photosensitizers
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DOI：
10.1089/clm.1998.16.81
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发表时间：
1998-04-01
期刊：
影响因子：
--
通讯作者：
Wilson, BC
中科院分区：
文献类型：
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作者：
Lilge, L;Wilson, BC
采用光动力学阈值模型，研究了四种不同光敏剂对正常脑组织和颅内肿瘤的颅内光动力学治疗（PDT）的有效性。摘要：目前正在研究PDT作为颅内肿瘤手术切除和/或放疗的辅助治疗。虽然已经注意到治疗可能的神经毒性副作用，但只有有限的临床前数据量化PDT后颅内正常和肿瘤组织的反应。材料和方法：四种光敏剂，Photofrin，5-氨基乙酰丙酸（ALA）诱导的原卟啉TX（PpIX），锡乙基黄嘌呤（SnET（2））和氯铝酞菁（AlClPc）的光动力学阈值剂量值，通过测量光通量分布，组织中的光敏剂浓度和PDT后组织学确定的坏死程度来确定。这些测量是在正常兔脑和颅内植入癌（VX 2）。结果如下：对于Photofrin、AlClPc和SnET（2）（乳剂递送载体），正常灰质和白色物质对PDT非常敏感，显示出比VX 2-肿瘤显著更低的阈值剂量值。对于ALA诱导的PpIX和SnET（2）锡脂质体），观察到非常少或没有白色物质损伤。此外，ALA-PpIX在白色物质中的浓度显著低于皮质和肿瘤中的浓度。缺乏血脑屏障的正常脑结构显示所有光敏剂的高摄取，因此在PDT期间有附带损伤的风险。结论：对于大多数成人颅内肿瘤的临床PDT，ALA诱导的PpIX似乎是有希望的，SnET（2）（脂质体）具有选择性肿瘤破坏的潜力，相对保留白色物质。如果在PDT过程中暴露于光，其他正常脑结构以及其他光敏剂的白色物质也有附带损伤的风险。
The effectiveness of four different photosensitizers for intracranial photodynamic therapy (PDT) of normal brain tissues and an intracranial tumor was investigated in rabbits, using the photodynamic threshold model. Summary: PDT is currently being investigated as an adjuvant treatment to surgical resection and/or radio chemotherapy of intracranial neoplasms. While possible neurotoxic side effects of the treatment have been noted, only limited preclinical data quantifying the response of intracranial normal and tumor tissues following PDT are available. Materials and Methods: The photodynamic threshold dose values for the four photosensitizers, Photofrin, 5-aminolevulinic acid (ALA)-induced Protoporphyrin TX (PpIX), Tin Ethyl Etiopurpurin (SnET(2)), and chloroaluminum phthalocyanine (AlClPc), were determined using measured light fluence distributions, photosensitizer concentration in tissue, and histologically-determined extent of necrosis following PDT. These measurements were made in normal rabbit brain and in an intracranially-implanted carcinoma (VX2). Results: For Photofrin, AlClPc, and SnET(2) tin an emulsion delivery vehicle) normal grey and white matter were very sensitive to PDT, showing a significantly lower threshold dose value than VX2-tumor. For ALA-induced PpIX and SnET(2) tin liposome) very little or no white matter damage was observed. Additionally, ALA-PpIX showed significantly lower concentration in white matter than in cortex and tumor, Normal brain structures lacking a blood-brain barrier showed high uptake of all photosensitizers and, hence, are at risk of collateral damage during PDT. Conclusions: For clinical PDT of most adult intracranial neoplasms ALA-induced PpIX appears to be promising, and SnET(2) (liposomal) has potential for selective tumor destruction with relative sparing of white matter. Other normal brain structures and, for the other photosensitizers, also white matter are at risk of collateral damage, if exposed to light during PDT.