title: Efficacy of intravenous delta-aminolaevulinic acid photodynamic therapy on rabbit papillomas.
abstract: 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.
authors.affiliation: Department of Otolaryngology, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Lofgren
authors.forename: A M
authors.initials: AM
authors.lastname: Ronn
authors.forename: M
authors.initials: M
authors.lastname: Nouri
authors.forename: C J
authors.initials: CJ
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Yoo
authors.forename: B M
authors.initials: BM
authors.lastname: Steinberg
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D010212:Papilloma / Q000188:drug therapy*; D010778:Photochemotherapy; D011524:Protoporphyrins / Q000097:blood; D011817:Rabbits; D012867:Skin / Q000187:drug effects
chemical_list: D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX