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5-氨基酮戊酸诱导的原卟啉IX在原位大鼠膀胱肿瘤模型中的生物分布及光毒性

Biodistribution and phototoxicity of 5-aminolevulinic acid-induced PpIX in an orthotopic rat bladder tumor model.

作者信息

Iinuma S, Bachor R, Flotte T, Hasan T

机构信息

Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston.

出版信息

J Urol. 1995 Mar;153(3 Pt 1):802-6.

PMID:7861543
Abstract

5-Aminolevulinic acid (ALA) is a precursor of heme biosynthesis. In the penultimate step of this biosynthesis, protoporphyrin IX (PpIX), an effective photosensitizer, is generated. In this study, the biodistribution and photodynamic effect of ALA-induced PpIX were investigated in an orthotopic rat bladder tumor model. A quantitative comparison of PpIX biodistribution by extraction and fluorescence spectroscopy following intravenous and intravesical administration of ALA was made. The tumor to normal bladder wall ratio was 2:1 at 4 hours for both delivery modes. Fluorescence microscopy demonstrated predominantly cellular rather than stromal PpIX fluorescence. Phototoxicity, evaluated 4 hours after ALA administration, was light dose-dependent with the most efficient tumor necrosis being observed upon 150 J/cm.2 of 630 nm. irradiation. These data suggest that optimized photodynamic therapy with ALA-induced PpIX may be an alternative treatment for superficial bladder carcinoma.

摘要

5-氨基酮戊酸(ALA)是血红素生物合成的前体。在该生物合成的倒数第二步中,会生成有效的光敏剂原卟啉IX(PpIX)。在本研究中,在原位大鼠膀胱肿瘤模型中研究了ALA诱导的PpIX的生物分布和光动力效应。对静脉内和膀胱内给予ALA后通过萃取和荧光光谱法对PpIX生物分布进行了定量比较。两种给药方式下,4小时时肿瘤与正常膀胱壁的比率均为2:1。荧光显微镜检查显示主要是细胞内而非基质中的PpIX荧光。在给予ALA 4小时后评估的光毒性呈光剂量依赖性,在630 nm、150 J/cm²照射时观察到最有效的肿瘤坏死。这些数据表明,用ALA诱导的PpIX进行优化的光动力疗法可能是浅表性膀胱癌的一种替代治疗方法。

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