Tope W D, Ross E V, Kollias N, Martin A, Gillies R, Anderson R R
Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.
Photochem Photobiol. 1998 Feb;67(2):249-55. doi: 10.1562/0031-8655(1998)067<0249:pifiib>2.3.co;2.
Limited depth of penetration significantly limits photodynamic therapy of nodular basal cell carcinoma (BCC) using topical delta (5)-aminolevulinic acid (ALA). To demonstrate safety and efficacy of orally administered ALA in inducing endogenous protoporphyrin IX (PpIX) production in BCC, 13 patients with BCC ingested ALA in a dose-escalation protocol. All dose ranges (10, 20 or 40 mg/kg single doses) resulted in formation of PpIX in human skin and BCC, measurable by in vivo fluorescence spectrophotometry. The PpIX fluorescence peaked in tumors before normal adjacent skin from 1 to 3 h after ALA ingestion. Gross fluorescence imaging of ex vivo specimens revealed greater PpIX fluorescence in tumor than normal skin only at the 40 mg/kg dose. Fluorescence microscopy confirmed this finding by showing distinct, full-thickness PpIX fluorescence in all subtypes of BCC only after ALA given at 40 mg/kg. Side effects were dose dependent and self limited. Photosensitivity lasting less than 24 h and nausea coinciding with peak skin PpIX fluorescence occurred at 20 and 40 mg/kg doses. After 40 mg/kg ALA, serum hepatic enzyme levels rose to a maximum within 24 h, then resolved over 1-3 weeks. Transient bilirubinuria occurred in two patients.
穿透深度有限显著限制了使用局部δ（5）-氨基乙酰丙酸（ALA）对结节性基底细胞癌（BCC）进行光动力治疗。为了证明口服ALA在诱导BCC内源性原卟啉IX（PpIX）生成中的安全性和有效性，13例BCC患者按照剂量递增方案摄入ALA。所有剂量范围（10、20或40mg/kg单次剂量）均导致人皮肤和BCC中形成PpIX，可通过体内荧光分光光度法测量。摄入ALA后1至3小时，PpIX荧光在肿瘤中达到峰值，高于相邻正常皮肤。离体标本的总体荧光成像显示，仅在40mg/kg剂量下，肿瘤中的PpIX荧光高于正常皮肤。荧光显微镜检查证实了这一发现，即在给予40mg/kg的ALA后，所有BCC亚型中均出现明显的全层PpIX荧光。副作用具有剂量依赖性且为自限性。20和40mg/kg剂量时出现持续时间少于24小时的光敏反应以及与皮肤PpIX荧光峰值同时出现的恶心。给予40mg/kg的ALA后，血清肝酶水平在24小时内升至最高，然后在1至3周内恢复正常。两名患者出现短暂性胆红素尿。
