Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring.
OBJECTIVE
The aim of this study was to determine whether 2 photosensitizers, benzoporphyrin-derivative monoacid ring and 5-aminolevulinic acid, are selectively absorbed by dysplastic cervical cells after topical administration.


METHODS
This phase I clinical trial involved 18 women with biopsy-proven cervical intraepithelial neoplasia at the Beckman Laser Institute, Irvine, Calif. Colposcopically directed cervical biopsy specimens obtained after 1.5, 3, or 6 hours of exposure to a randomly assigned photosensitizer were evaluated for selective drug absorption with hematoxylin and eosin staining and fluorescence microscopy.


RESULTS
After exposure to 5-aminolevulinic acid, cervical tissue showed maximal fluorescence in dysplastic cells relative to normal cells, with negligible stromal fluorescence. According to our detection methods benzoporphyrin-derivative monoacid ring demonstrated nonselective, diffusion-driven uptake, with fluorescence appearing in the superficial cells, followed by nonselective drug absorption in the remaining cells and stroma of the epithelium.


CONCLUSIONS
Our data demonstrated selective absorption of 5-aminolevulinic acid by dysplastic cervical cells. This agent therefore represents a promising photosensitizing prodrug for the treatment of cervical intraepithelial neoplasia with photodynamic therapy.
Keefe
K A
KA
Department of Obstetrics and Gynecology, University of California Irvine Medical Center, USA.
Chahine
E B
EB
DiSaia
P J
PJ
Krasieva
T B
TB
Lin
F
F
Berns
M W
MW
Tadir
Y
Y
D000042:Absorption; D000622:Aminolevulinic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002584:Cervix Uteri / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000473:pathology
D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D; D000622:Aminolevulinic Acid