[Fluorescence diagnosis with 5-ALA thermogel of cervical intraepithelial neoplasia]

To study the pharmacokinetics and selectivity of 5-aminolevulinic acid (5-ALA) from 5-ALA thermolabile gel formulation in cervical intraepithelial neoplasia (CIN). The novel thermogel Pluronic F127 is liquid at cold temperatures and turns into a gel-like consistency at body temperature, thereby improving adhesion of 5-ALA to the cervix uteri.

27 female patients with CIN 1-3 were included in this study. Thirty minutes to 12 h before conisation, 10 mL of thermo-gel containing either 4, 10, or 20% of 5-ALA were topically applied to the cervix. Biopsies were taken from the lesions as well as normal surrounding epithelial tissue for histological examination, fluorescence microscopy and spectrometry.

The thermogel Pluronic F127 was easy to handle and proved reliable as vehicle carrier. 5-ALA induced porphyrin fluorescence was maximal after application of 10% 5-ALA thermogel. We observed the higher porphyrin fluorescence intensity within the CIN lesions (1,116 +/- 241 AU), as compared to normal adjacent epithelium (704 +/- 166 AU). This difference was statistically significant (p < 0.05). Four to six hours after application, porphyrin fluorescence in dysplastic epithelium reached maximal intensity, and tumor selectivity was the highest in CIN 3 achieving a tumor-to-normal ratio of 3.5. Compared to other studies employing 5-ALA, the thermogel preparation of 5-ALA leads to twofold increase in the porphyrin selectivity.

The thermogel Pluronic F127 seems to improve the local cervical drug application. Based on these results, we recommend the application of a 10% 5-ALA thermogel formulation 4-6 h prior to photodynamic therapy in CIN.