title: Detection of female lower genital tract dysplasia using orally administered 5-aminolevulinic acid induced protoporphyrin IX: a preliminary study.
abstract: OBJECTIVE
  Previous studies have suggested that 5-aminolevulinic acid (ALA) may be used topically on the cervix to allow optical detection of cervical dysplasia, based on the fluorescence of protoporphyrin IX (PpIX) synthesized in situ from ALA. However, the uniformity of distribution of topically applied PpIX and the sensitivity and specificity of detection are not optimal. The current study was undertaken to demonstrate the feasibility of administering ALA by mouth (po) with the hypothesis that systemic administration might provide a more reliable diagnostic tool.
  
  
  METHODS
  Oral ALA was administered to 14 patients with abnormal Pap smears in a dose- and time-intensity design. Institutional review board approval was obtained. A starting dose of 10 mg/kg of po ALA was administered and colposcopy was performed in 3 patients at 1 h, 3 patients at 2 h, 6 patients at 3 h, and 2 patients at 4 h. The study was written with the intent to increase the dose in 10 mg/kg increments if fluorescence was not detected; however, fluorescence was detected at the first dose level. Liver function tests were checked pre and post ALA and follow-up telephone calls were made regarding possible side effects. Both white and blue light colposcopy examinations were performed by two blinded clinicians and biopsies of all abnormal areas were performed.
  
  
  RESULTS
  All patients tolerated po ALA well, with no systemic side effects. At the 10 mg/kg dose there was no reported nausea or photosensitivity. Optimal fluorescence was achieved at the 3-h time point, with quenching noted at the 4-h time point. Excellent absorption was documented with fluorescence of the lip demonstrated with Wood's lamp. In some cases fluorescence correlated with dysplasia on biopsy.
  
  
  CONCLUSIONS
  5-ALA given via the po route and at the dose and time period studied is well tolerated and affords fluorescence of the cervix. Future study is needed to demonstrate the successful identification of dysplastic lesions, with the ultimate goal of treating dysplasia of the lower genital tract with 5-ALA and light therapy.
authors.affiliation: Vincent Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. lduska@partners.org
authors.forename: Linda R
authors.initials: LR
authors.lastname: Duska
authors.forename: Joanne
authors.initials: J
authors.lastname: Wimberly
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Deutsch
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ortel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Haas
authors.forename: Karen
authors.initials: K
authors.lastname: Houck
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000284:Administration, Oral; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D065006:Papanicolaou Test; D010778:Photochemotherapy / Q000379:methods*; D011524:Protoporphyrins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014626:Vaginal Smears
chemical_list: D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX