Combination effect of photofrin and ALA for photodynamic therapy on experimental tongue squamous cell carcinoma in mice

5-氨基乙酰丙酸（ALA）诱导的原卟啉-IX（Pp-IX）已在口腔癌治疗的光动力疗法（PDT）中用作光敏剂。本研究通过分析舌肿瘤组织中的Pp-IX荧光来探讨ALA的最佳给药方法。在小鼠移植性舌癌中，经腹腔、口服或局部施用ALA后，将Pp-IX强度与正常舌中的强度进行比较。还检查了ALA与铁螯合剂（甲磺酸去铁胺）联合给药的效果。铁螯合剂在ALA给药前1、2、3 h或同时给药。用分光光度计测定舌肿瘤组织中Pp-IX的浓度（μM），发现口服ALA后5 h，Pp-IX在舌肿瘤组织中的蓄积量最大。在口服ALA前1小时腹腔注射铁螯合剂，舌肿瘤组织中Pp-IX的蓄积显著增加。结果表明，ALA联合铁螯合剂口服给药组的Pp-IX强度在ALA口服给药后3 h达到峰值，约为单纯ALA给药组的2倍，提示ALA联合铁螯合剂口服给药是ALA-PDT治疗口腔癌最有效的给药方式。这种方法有望提高治疗效果，减少副作用和治疗时间，因为铁螯合剂的组合增加了Pp-IX强度，并加速了Pp-IX在肿瘤组织中的积累和排泄。

5-aminolevulinic acid (ALA)-induced protoporphyrin-IX (Pp-IX) has been used as a photosensitizer in photodynamic therapy (PDT) for oral cancer treatment. This study investigates the optimal method of administrating ALA by analyzing Pp-IX fluorescence in tongue tumor tissue. The influence of iron chelator on Pp-IX accumulation in the tumor tissue is also examined.Pp-IX intensities in the mouse transplanted tongue cancer were compared with those in normal tongue after intraperitoneal, oral, or topical administration of ALA. The effects of ALA in combination with iron chelator (desferoxamine mesilate) administration were also examined. Iron chelator was administrated simultaneously or 1, 2, or 3hr before administration of ALA. Pp-IX concentration(μM) was obtained from a serial frozen sections of each sample by using a spectrophotometer.Maximum Pp-IX accumulation in the tongue tumor tissue was seen at 5h after the oral administration of ALA. When the iron chelator was administrated intraperitoneally 1hr before oral administration of ALA, Pp-IX accumulation in the tongue tumor tissues was remarkable enhanced. Pp-IX intensity in this iron chelator combination group peaked at 3h after oral administration of ALA, which was about twice as high as that in the tumor group given ALA alone without iron chelator.These results suggested that oral administration was the most effective administration method for ALA in combination with iron chelator in ALA-PDT for oral cancer. This method would be expected to enhance the therapeutic effect and to reduce the side effects and treatment time because the combination of iron chelator increased the Pp-IX intensity and hastened the Pp-IX accumulation and excretion in the tumor tissue.