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）已被用作光动力疗法（PDT）治疗口腔癌的光敏剂。本研究通过分析舌肿瘤组织中Pp-IX荧光来探讨ALA的最佳给药方法。铁螯合剂对肿瘤组织中Pp-IX积累的影响也进行了研究。通过腹腔、口服或局部给药ALA，比较小鼠移植舌癌与正常舌癌的Pp-IX强度。还研究了ALA与铁螯合剂（甲磺酸去铁胺）联合使用的效果。铁螯合剂同时给药或在ALA给药前1、2、3小时给药。用分光光度计从每个样品的连续冷冻切片中获得Pp-IX浓度（μM）。口服ALA后5h， Pp-IX在舌肿瘤组织中积累最多。在口服ALA前1h腹腔注射铁螯合剂，Pp-IX在舌肿瘤组织中的蓄积明显增强。该铁螯合剂联合组的Pp-IX强度在口服ALA后3h达到峰值，约为单独给予ALA而不使用铁螯合剂的肿瘤组的2倍。提示口服ALA联合铁螯合剂是口腔癌ALA- pdt治疗中最有效的给药方式。联用铁螯合剂可增加肿瘤组织中Pp-IX的浓度，加速其在肿瘤组织中的积累和排泄，有望提高治疗效果，减少副作用，缩短治疗时间。

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.