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。本研究通过对舌癌组织中PP-IX荧光的分析，探讨ALA给药的最佳方法。研究了铁络合剂对PP-IX在肿瘤组织中蓄积的影响。比较了小鼠舌癌移植瘤和正常舌体内注射ALA后PP-IX的表达强度。同时观察ALA与铁络合剂(甲磺酸去铁胺)联合给药的疗效。同时给予铁络合剂，或在给药前1、2、3小时给予铁络合剂。用分光光度计测各标本冰冻切片中PP-IX的浓度(μM)，口服ALA后5h，PP-IX在舌肿瘤组织中积聚最大。在口服ALA前1小时给予铁络合剂，可显著增加PP-IX在舌癌组织中的蓄积。ALA铁络合剂联合用药组PP-IX在口服ALA后3h达到高峰，约为单纯ALA组的2倍，提示口服ALA联合铁络合剂是ALA-PDT治疗口腔癌最有效的给药方式。由于铁络合剂的联合应用增加了PP-IX的强度，加速了PP-IX在肿瘤组织中的蓄积和排泄，因此有望提高治疗效果，减少副作用和治疗时间。

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.