title: Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of California Irvine Medical Center, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Keefe
authors.forename: E B
authors.initials: EB
authors.lastname: Chahine
authors.forename: P J
authors.initials: PJ
authors.lastname: DiSaia
authors.forename: T B
authors.initials: TB
authors.lastname: Krasieva
authors.forename: F
authors.initials: F
authors.lastname: Lin
authors.forename: M W
authors.initials: MW
authors.lastname: Berns
authors.forename: Y
authors.initials: Y
authors.lastname: Tadir
mesh_terms: 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
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D; D000622:Aminolevulinic Acid