EFFICACY OF INTRAVENOUS DELTA-AMINOLEVULINIC-ACID PHOTODYNAMIC THERAPY ON RABBIT PAPILLOMAS

Endogenously induced protoporphyrin IX (PPIX), a metabolite of delta-a minolaevulinic acid (ALA), has been evaluated as a photosensitising ag ent for destruction of papillomas in cottontail rabbit papillomavirus- infected Dutch belted and New Zealand rabbits. Three factors were eval uated: (1) relative retention ratio of drug in normal tissue, papillom a and plasma over time; (2) tissue tolerance to treatment factors; and (3) efficacy of treatment protocol. Three drug doses of ALA were exam ined: 50, 100 and 200 mg kg(-1). Actual PPIX concentrations in tissue and plasma were determined spectrophotofluorometrically. The optimal t reatment time occurred 3-6 h post ALA injection. The highest PPIX conc entration ratio between papilloma and normal skin was 6:1. Different l ight 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 mm. E fficacy 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 mm (3) and the plasma concentration of PPIX immediately before exposure w as above 500 mu g ml(-1). The short time between injection and treatme nt and high efficacy, together with PPIX disappearance from plasma and tissue within 24 h, make injected ALA a highly attractive drug for ph otodynamic therapy.