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.
Institute for Surgical Research, Ludwig-Maximilians-University, Klinikum Grosshadern, Munich, Germany.
S A
SA
Pahernik
A
A
Botzlar
P
P
Hillemanns
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M
Dellian
M
M
Kirschstein
C
C
Abels
M
M
Korell
J
J
Mueller-Hoecker
M
M
Untch
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AE
Goetz
D000328:Adult; D000622:Aminolevulinic Acid / Q000493:pharmacokinetics* / Q000494:pharmacology; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D019092:Conization; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010778:Photochemotherapy; D011166:Porphyrins / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D011166:Porphyrins; D000622:Aminolevulinic Acid