title: Pharmacokinetics and selectivity of porphyrin synthesis after topical application of hexaminolevulinate in patients with cervical intraepithelial neoplasia.
abstract: OBJECTIVE
  Photodynamic therapy has the potential of a minimal invasive outpatient procedure for CIN patients at reproductive ages. The purpose of this study was to examine the pharmacokinetics and selectivity of porphyrin synthesis after topical application of hexaminolevulinate (HAL) in patients with cervical intraepithelial neoplasia (CIN).
  
  
  METHODS
  Twenty-four women with CIN 1-3 received 4 mmol/L or 10 mmol/L HAL dissolved in thermolabile pluronic F 127 gel topically 5-720 minutes before surgical conization. The microscopic fluorescence pattern was quantified by ex vivo fluorescence spectroscopy at a wavelength of 635 nm and semiquantitatively by digital image analysis from cryosections.
  
  
  RESULTS
  With 4 and 10 mmol/L HAL, porphyrin fluorescence intensity increased over time, reaching a peak after 180-540 minutes application intervals in CIN and normal epithelium. However, the peak was much more pronounced in CIN than in normal tissues. The fluorescence intensity with 10 mmol/L was significantly higher than that with 4 mmol/L in CIN tissues (P < .05). Maximum intensity could generally be detected in the lower layer of the epithelium.
  
  
  CONCLUSIONS
  HAL seems to be a promising molecule for fluorescence diagnosis. For further treatment studies, we recommend application of 10 mmol/L HAL 300-540 minutes before photodynamic therapy in CIN.
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany. Hillemanns.Peter@mh-hannover.de
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wang
authors.forename: Hermann
authors.initials: H
authors.lastname: Hertel
authors.forename: Vaagn
authors.initials: V
authors.lastname: Andikyan
authors.forename: Marija
authors.initials: M
authors.lastname: Hillemanns
authors.forename: Herbert
authors.initials: H
authors.lastname: Stepp
authors.forename: Philipp
authors.initials: P
authors.lastname: Soergel
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D005453:Fluorescence; D006801:Humans; D008875:Middle Aged; D010778:Photochemotherapy; D011166:Porphyrins / Q000032:analysis* / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*
chemical_list: D002250:Carbon Radioisotopes; D011166:Porphyrins; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester