Orenstein A, Kostenich G, Roitman L, Shechtman Y, Kopolovic Y, Ehrenberg B, Malik Z
Department of Plastic Surgery, Sheba Medical Centre, Tel Hashomer, Israel.
Br J Cancer. 1996 Apr;73(8):937-44. doi: 10.1038/bjc.1996.185.
An in vivo study of tissue distribution kinetics and photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA), chlorin e6 (Chl) and Photofrin (PII) was performed to evaluate the selectivity of porphyrin accumulation and tissue damage effects in a tumour model compared with normal tissue. C26 colon carcinoma of mice transplanted to the foot was used as a model for selectivity assessment. Fluorescence measurements of porphyrin accumulation in the foot bearing the tumour and in the normal foot were performed by the laser-induced fluorescence (LIF) system. A new high-intensity pulsed light delivery system (HIPLS) was used for simultaneous irradiation of both feet by light in the range of 600-800 nm, with light doses from 120 to 300 J cm-2 (0.6 J cm-2 per pulse, 1 Hz). Photoirradiation was carried out 1 h after injection of ALA, 3 h after injection of Chl and 24 h after injection of PII. A ratio of porphyrin accumulation in tumour vs normal tissue was used as an index of accumulation selectivity for each agent. PDT selectivity was determined from the regression analysis of normal and tumour tissue responses to PDT as a function of the applied light dose. A normal tissue damage index was defined at various values (50, 80 and 100%) of antitumour effect. The results of the LIF measurements revealed different patterns of fluorescence intensity in tumour and normal tissues for ALA-induced protoporphyrin IX (ALA-PpIX), Chl and PII. The results of PDT demonstrated the differences in both anti-tumour efficiency and normal tissue damage for the agents used. The selectivity of porphyrin accumulation in the tumour at the time of photoirradiation, as obtained by the LIF measurements, was in the order ALA-PpIX > Chl > PII. PDT selectivity at an equal value of anti-tumour effect was in the order Chl > ALA-PpIX > PII. Histological examination revealed certain differences in structural changes of normal skin after PDT with the agents tested. The results of PDT selectivity assessment with respect to differences in mechanisms of action for ALA, Chl and PII are discussed.
进行了一项体内研究，以评估使用5-氨基乙酰丙酸（ALA）、氯e6（Chl）和光敏素（PII）时的组织分布动力学和光动力疗法（PDT），并与正常组织相比，评估肿瘤模型中卟啉积累的选择性和组织损伤效应。将移植到足部的小鼠C26结肠癌用作选择性评估模型。通过激光诱导荧光（LIF）系统对荷瘤足部和正常足部的卟啉积累进行荧光测量。一种新型高强度脉冲光输送系统（HIPLS）用于同时对双足进行600 - 800 nm范围内的光照射，光剂量为120至300 J/cm²（每脉冲0.6 J/cm²，1 Hz）。在注射ALA后1小时、注射Chl后3小时和注射PII后24小时进行光照射。肿瘤与正常组织中卟啉积累的比率用作每种药物积累选择性的指标。根据正常组织和肿瘤组织对PDT的反应作为所施加光剂量的函数进行回归分析来确定PDT选择性。在不同抗肿瘤效果值（50%、80%和100%）下定义正常组织损伤指数。LIF测量结果显示，ALA诱导的原卟啉IX（ALA-PpIX）、Chl和PII在肿瘤组织和正常组织中的荧光强度模式不同。PDT结果表明所使用药物在抗肿瘤效率和正常组织损伤方面存在差异。通过LIF测量获得的光照射时肿瘤中卟啉积累的选择性顺序为ALA-PpIX > Chl > PII。在相等抗肿瘤效果值下的PDT选择性顺序为Chl > ALA-PpIX > PII。组织学检查显示，用所测试药物进行PDT后，正常皮肤的结构变化存在一定差异。讨论了关于ALA、Chl和PII作用机制差异的PDT选择性评估结果。
