Photodynamic therapy with 5-aminolevulinic acid: a promising concept for the treatment of cutaneous tumors.
Photodynamic therapy with 5-aminolevulinic acid: a promising concept for the treatment of cutaneous tumors.
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5-氨基乙酰丙酸光动力疗法：治疗皮肤肿瘤的一个有前途的概念。
作者：
P. Wolf;H. Kerl
光动力疗法（PDT）是一种无创疗法，首先应用光敏物质（光敏剂），然后用可见光激发[1-3]。光敏剂选择性地积聚在某些细胞、组织和肿瘤中，它们的光活化导致细胞毒性物质的释放，进而破坏组织。 PDT 的临床应用由 Dougherty 等人在 20 世纪 70 年代首创[11]。此后，PDT已被实验性地用于治疗各种肿瘤，包括中枢神经、食道、胃肠道、泌尿生殖、支气管内、头颈和皮肤恶性肿瘤[2, 3]。最近，Kennedy 等人[4, 5]介绍了一种新的 PDT 方法，涉及内源性卟啉的光敏化。这种形式的 PDT 使用 5-氨基乙酰丙酸 (ALA)，它是血红素生物合成途径中卟啉的前体。自然地，ALA 的产生受到负反馈机制的控制，其中游离血红素的存在会抑制 ALA 的合成 [4, 5]，但是，如果使用过量的外源性 ALA，则可以绕过这种反馈抑制，导致内源性卟啉（主要是原卟啉 IX）的积聚 (6, 7]。局部应用在水溶液中，ALA 很容易穿过异常层的表皮与标准 PDT 相比，标准 PDT 中静脉注射基于卟啉的光敏剂（例如 Photofrin®）会在几周内导致普遍且通常严重的光敏性，而局部使用 ALA 后，内源性卟啉的光敏性通常会在 24 天内消失| 4, 8] 或全身 [7]。 h. 这使得 ALA-PDT 成为一种实用的治疗方式，在推出几年后，ALA-PDT 的首次临床研究报告了局部应用日光角化病和浅表皮肤癌（包括浅表鳞状细胞癌 [4, 8]、鲍文氏病 [9, 10] 和浅表基底细胞癌）的良好反应率和优异的美容效果。 8-10]，
Photodynamic therapy (PDT) is a noninvasive modality in which photosensitizing substances (photosensitizers) are first applied, and then excited with visible light [1-3]. Pho tosensitizers selectively accumulate in certain cells, tissues, and tumors, and their photoactivation leads to the release of cytotoxic substances, which in turn destroys tissue. The clinical use of PDT was pioneered by Dougherty et al.[11 in the 1970s. Since then, PDT has been used experimentally to treat various tumors, including central nervous, esopha geal, gastrointestinal, genitourinary, endobronchial, head and neck, and skin malignancies [2, 3]. Recently, Kennedy et al.[4, 5] introduced a new ap proach to PDT involving photosensitization with endoge nous porphyrins. This form of PDT uses 5-aminolevulinic acid (ALA), a precursor of porphyrins in the biosynthetic pathway of heme. Naturally, the production of ALA is con trolled by a negative feedback mechanism in which the presence of free heme inhibits the synthesis of ALA [4, 5], However, if an excess of exogenous ALA is applied, this feedback inhibition can be bypassed, leading to a build-up of endogenous porphyrins, mainly protoporphyrin IX (6, 7], Topically applied in aqueous solution, ALA readily passes through the epidermis with an abnormal stratum corneum but not through normal epidermis, thus allowing the highly selective photosensitization of skin tumors [4, 3]. In contrast to standard PDT, in which the intravenous injection of porphyrin-based photosensitizers such as Photofrin® leads to generalized and often severe photosensitivity over several weeks [1], photosensitization with endogenous por phyrins after topical| 4, 8] or systemic [7] application ofALA usually vanishes within 24 h. This makes ALA-PDT a practical treatment modality, which, only a few years after its introduction, is used experimentally in many centers around the world. The first clinical studies of ALA-PDT reported good response rates and excellent cosmetic results for topical application in solar keratoses and superficial skin cancers, including superficial squamous cell carcino mas [4, 8], Bowen’s disease [9, 10] and superficial basal cell carcinomas [4, 8-10],