Lofgren L A, Ronn A M, Nouri M, Lee C J, Yoo D, Steinberg B M
Department of Otolaryngology, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.
Br J Cancer. 1995 Oct;72(4):857-64. doi: 10.1038/bjc.1995.424.
Endogenously induced protoporphyrin IX (PPIX), a metabolite of delta-aminolaevulinic acid (ALA), has been evaluated as a photosensitising agent for destruction of papillomas in cottontail rabbit papillomavirus-infected Dutch belted and New Zealand rabbits. Three factors were evaluated: (1) relative retention ratio of drug in normal tissue, papilloma and plasma over time; (2) tissue tolerance to treatment factors; and (3) efficacy of treatment protocol. Three drug doses of ALA were examined: 50, 100 and 200 mg kg-1. Actual PPIX concentrations in tissue and plasma were determined spectrophotofluorometrically. The optimal treatment time occurred 3-6 h post ALA injection. The highest PPIX concentration ratio between papilloma and normal skin was 6:1. Different light doses were investigated, using an injection to exposure interval of 3 h and an irradiance of 100 mW cm-2 at a wavelength of 630 nm. Efficacy without risk of significant damage to normal skin was obtained using 100-200 mg kg-1 ALA and 40-60 J cm-2. A long-term (3 months) cure rate of 82% was obtained with a single treatment, provided that papilloma depth did not exceed 8 mm, volume was not more than 1000 mm3 and the plasma concentration of PPIX immediately before exposure was above 500 micrograms ml-1. The short time between injection and treatment and high efficacy, together with PPIX disappearance from plasma and tissue within 24 h, make injected ALA a highly attractive drug for photodynamic therapy.
内源性诱导的原卟啉IX（PPIX）是δ-氨基乙酰丙酸（ALA）的一种代谢产物，已被评估为一种光敏剂，用于破坏感染棉尾兔乳头瘤病毒的荷兰带兔和新西兰兔的乳头瘤。评估了三个因素：（1）药物在正常组织、乳头瘤和血浆中的相对保留率随时间的变化；（2）组织对治疗因素的耐受性；（3）治疗方案的疗效。研究了三种ALA药物剂量：50、100和200mg kg-1。通过分光光度荧光法测定组织和血浆中的实际PPIX浓度。最佳治疗时间出现在ALA注射后3-6小时。乳头瘤与正常皮肤之间的最高PPIX浓度比为6:1。研究了不同的光剂量，注射至暴露间隔为3小时，波长630nm处的辐照度为100mW cm-2。使用100-200mg kg-1 ALA和40-60J cm-2可获得对正常皮肤无明显损伤风险的疗效。如果乳头瘤深度不超过8mm，体积不超过1000mm3，暴露前血浆中PPIX浓度高于500μg ml-1，单次治疗的长期（3个月）治愈率为82%。注射与治疗之间的时间短且疗效高，再加上PPIX在24小时内从血浆和组织中消失，使得注射ALA成为光动力治疗极具吸引力的药物。
