Pharmacokinetics and selectivity of porphyrin synthesis after topical application of hexaminolevulinate in patients with cervical intraepithelial neoplasia

Am J Obstet Gynecol. 2008 Mar;198(3):300.e1-7. doi: 10.1016/j.ajog.2007.07.045. Epub 2008 Feb 21.

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).

Study design: 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.

Conclusion: 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.

MeSH terms

  • Administration, Topical
  • Adult
  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / analogs & derivatives*
  • Aminolevulinic Acid / pharmacokinetics
  • Carbon Radioisotopes / administration & dosage*
  • Carbon Radioisotopes / pharmacokinetics*
  • Female
  • Fluorescence
  • Humans
  • Middle Aged
  • Photochemotherapy*
  • Porphyrins / analysis*
  • Porphyrins / biosynthesis
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Neoplasms / diagnosis*

Substances

  • Carbon Radioisotopes
  • Porphyrins
  • Aminolevulinic Acid
  • 5-aminolevulinic acid hexyl ester