Pharmacokinetics and selectivity of aminolevulinic acid–induced porphyrin synthesis in patients with cervical intra‐epithelial neoplasia

Photodynamic therapy (PDT), due to its tumor selectivity, represents an alternative approach to diagnose and treat cervical intra‐epithelial neoplasia (CIN) without altering normal surrounding tissue. Our aim was to investigate the pharmacokinetics and the selectivity of 5‐aminolevulinic acid (5‐ALA)–induced porphyrin fluorescence after topical administration, to obtain basic clinical data for future diagnostic fluorescence imaging and PDT protocols for CIN. Twenty‐eight non‐pregnant women with a cytological diagnosis of low‐grade or high‐grade squamous intra‐epithelial lesions were included. An aqueous solution containing 3% 5‐ALA was topically applied 1 to 6 hrs prior to conization using a cervical cap. After excision, porphyrin‐induced fluorescence was quantified in dysplastic (n = 14) and normal epithelium (n = 28) by means of quantitative fluorescence microscopy. High values of porphyrin fluorescence were found in squamous epithelium between 150 and 450 min, with a maximum at 300 min following administration of 5‐ALA. Ratios of porphyrin fluorescence of dysplastic vs. surrounding normal epithelium were 1.3 and 1.21 for CIN 1 (n = 3) and CIN 2 (n = 3), respectively. In CIN 3 patients (n = 8), this ratio was 2.35; the best selectivity of 5‐ALA‐induced porphyrin fluorescence in CIN 3 lesions (ratio 3) was observed with a topical administration time of between 150 and 250 min. Our results demonstrate that patients with CIN 3 show higher 5‐ALA‐induced fluorescence compared with normal epithelium. The optimal administration time of topically applied 5‐ALA was between 3 and 4 hr. Our data suggest that topical ALA‐PDT and photodynamic diagnosis might be suitable for detecting CIN. Int. J. Cancer 78:310–314, 1998.© 1998 Wiley‐Liss, Inc.