Pass H I
Thoracic Oncology Section, NCI/NIH, Bethesda, MD 20892.
J Natl Cancer Inst. 1993 Mar 17;85(6):443-56. doi: 10.1093/jnci/85.6.443.
In photodynamic therapy (PDT), a sensitizer, light, and oxygen are used to cause photochemically induced cell death. The mechanism of cytotoxicity involves generation of singlet oxygen and other free radicals when the light-excited sensitizer loses or accepts an electron. Although selective retention of sensitizer by malignant tissue is seen in vivo, the mechanisms for this sensitizer targeting remain unclear. The first-generation sensitizers are porphyrin based and vary in lipophilicity and hydrophilicity. Targeting of the vasculature seems to be a prominent feature of the cytotoxic effect of these sensitizers in vivo, with resulting necrosis. Treatment depth varies with the wavelength of light that activates the sensitizer used, and the second-generation sensitizers are activated at longer wavelengths, allowing for a 30% increase in treatment depths. The selectivity of targeting can be increased when the sensitizer is delivered with the use of liposomes or monoclonal antibodies specific for tumor antigens. Studies have demonstrated direct effects of PDT on immune effector cells, specifically those with lineage from macrophages or other monocytes. Clinically, this therapy has been chiefly used for palliation of endobronchial and esophageal obstruction, as well as for treatment of bladder carcinomas, skin malignancies, and brain tumors. The future of PDT rests in defining its use either as an intraoperative adjuvant to marginal surgical procedures or as a primary treatment for superficial malignancies. Phase III trials in esophageal cancer and lung cancer are in progress and will help in evaluation of whether Photofrin II, the most widely used sensitizer, can be added to the oncologic armamentarium, pending approval from the U.S. Food and Drug Administration.
在光动力疗法（PDT）中，一种敏化剂、光和氧气被用于引起光化学诱导的细胞死亡。细胞毒性机制涉及当光激发的敏化剂失去或接受一个电子时单线态氧和其他自由基的产生。尽管在体内可见恶性组织对敏化剂的选择性保留，但这种敏化剂靶向的机制仍不清楚。第一代敏化剂是以卟啉为基础的，在亲脂性和亲水性方面有所不同。靶向脉管系统似乎是这些敏化剂在体内细胞毒性作用的一个突出特征，会导致坏死。治疗深度随激活所用敏化剂的光的波长而变化，第二代敏化剂在更长波长下被激活，使治疗深度增加30%。当使用脂质体或针对肿瘤抗原的单克隆抗体递送敏化剂时，靶向的选择性可以提高。研究已经证明PDT对免疫效应细胞有直接作用，特别是那些源自巨噬细胞或其他单核细胞的细胞。临床上，这种疗法主要用于缓解支气管内和食管梗阻，以及治疗膀胱癌、皮肤恶性肿瘤和脑肿瘤。PDT的未来在于确定其作为术中辅助边缘性外科手术的用途，或者作为浅表恶性肿瘤的主要治疗方法。食管癌和肺癌的III期试验正在进行，这将有助于评估最广泛使用的敏化剂卟吩姆钠（Photofrin II）能否在获得美国食品药品监督管理局批准之前被纳入肿瘤治疗手段。
