脑胶质瘤光动力治疗及光敏剂引导手术的研究与临床应用进展

摘要

脑胶质瘤具有浸润性生长的特性和多原位复发的特点,最大程度安全切除肿瘤,并辅以有效的局部治疗可能会改善患者的预后.血卟啉衍生物(hematoporphyrin derivative,HpD)、5-氨基酮戊酸(5-aminolevulinic acid,5-ALA)等光敏剂进人体内后,能特异地聚集在脑胶质瘤组织中.此时用特定波长的光照射肿瘤组织,一方面激发出可探测的荧光从而定位肿瘤组织所在的位置,用于荧光引导的胶质瘤切除手术(fluorescence-guided surgery,FGS);另一方面可产生光化学反应,生成单线态氧,导致肿瘤细胞损伤,用于光动力学疗法(photodynamic therapy,PDT)治疗脑胶质瘤,而对正常组织基本无损伤.早期研究提示单次PDT治疗可在一定程度上延长脑胶质瘤患者的生存期,但自从替莫唑胺应用于脑胶质瘤的治疗以来,应用日渐减少.随后,更多地将5-ALAJ用于荧光引导手术以提高胶质瘤的切除程度,近年得到认可并逐步推广应用.%The prognosis of glioma remains poor because of the infiltrative nature and the high local relapse rate.The current goals for patients with gliomas is maximal safe resection and adjuvant therapy.Tumor-specific photosensitizer,such as hematoporphyrin derivative (HpD) 5-aminolevulinic acid (5-ALA),can be selective up-taken and accumulated in tumor tissue.Light with appropriate wavelength can penetrate tumor tissue and excite the photosensitizer.The excited photosensitizer within glioma cells permits fluorescence visualization of tumor tissue during surgery and has been introduced in treatment of glioma as fluorescence-guided surgery (FGS).On the other hand,the toxicity of singlet oxygen generated by the excited photosensitizer has been used as photodynamic therapy (PDT) in selective destruction of the tumor.Some reports demonstrated the usefulness of adding PDT as an intraoperative adjuvant therapy,but the complexity associated with its implementation and the introduction of TMZ prevented PDT from becoming a routine therapy.However,FGS using 5-ALA in patients with malignant brain tumors has surfaced globally and may become a useful tool in increasing the extent of resection in gliomas.