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光动力疗法疗效与光敏剂在肝脏中的非均一分布相关。

Non-homogeneous liver distribution of photosensitizer and its consequence for photodynamic therapy outcome.

机构信息

Instituto de Física de São Carlos, Universidade de São Paulo, Av Trabalhador São-carlense, 400, CEP 13566-590, São Carlos, SP, Brazil.

出版信息

Photodiagnosis Photodyn Ther. 2010 Sep;7(3):189-200. doi: 10.1016/j.pdpdt.2010.07.002. Epub 2010 Jul 31.

DOI:10.1016/j.pdpdt.2010.07.002
PMID:20728844
Abstract

BACKGROUND

Photodynamic therapy is mainly used for treatment of malignant lesions, and is based on selective location of a photosensitizer in the tumor tissue, followed by light at wavelengths matching the photosensitizer absorption spectrum. In molecular oxygen presence, reactive oxygen species are generated, inducing cells to die. One of the limitations of photodynamic therapy is the variability of photosensitizer concentration observed in systemically photosensitized tissues, mainly due to differences of the tissue architecture, cell lines, and pharmacokinetics. This study aim was to demonstrate the spatial distribution of a hematoporphyrin derivative, Photogem, in the healthy liver tissue of Wistar rats via fluorescence spectroscopy, and to understand its implications on photodynamic response.

METHODS

Fifteen male Wistar rats were intravenously photosensitized with 1.5mg/kg body weight of Photogem. Laser-induced fluorescence spectroscopy at 532 nm-excitation was performed on ex vivo liver slices. The influence of photosensitizer surface distribution detected by fluorescence and the induced depth of necrosis were investigated in five animals.

RESULTS

Photosensitizer distribution on rat liver showed to be greatly non-homogeneous. This may affect photodynamic therapy response as shown in the results of depth of necrosis.

CONCLUSIONS

As a consequence of these results, this study suggests that photosensitizer surface spatial distribution should be taken into account in photodynamic therapy dosimetry, as this will help to better predict clinical results.

摘要

背景

光动力疗法主要用于治疗恶性病变,其基于光敏剂在肿瘤组织中的选择性定位,随后用光照射与光敏剂吸收光谱相匹配的波长。在分子氧存在的情况下,会产生活性氧物种,诱导细胞死亡。光动力疗法的一个局限性是在系统性光敏组织中观察到的光敏剂浓度的可变性,这主要是由于组织结构、细胞系和药代动力学的差异。本研究旨在通过荧光光谱法证明血卟啉衍生物 Photogem 在 Wistar 大鼠健康肝脏组织中的空间分布,并了解其对光动力反应的影响。

方法

15 只雄性 Wistar 大鼠经静脉内给予 1.5mg/kg 体重的 Photogem 光敏化。对离体肝切片进行 532nm 激发的激光诱导荧光光谱检测。在 5 只动物中研究了荧光检测到的光敏剂表面分布和诱导的坏死深度的影响。

结果

大鼠肝脏中的光敏剂分布极不均匀。这可能会影响光动力治疗的反应,正如坏死深度的结果所示。

结论

鉴于这些结果,本研究表明,在光动力疗法剂量学中应考虑光敏剂表面空间分布,因为这将有助于更好地预测临床结果。

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