Photomedicine of the endometrium: experimental concepts

Gynaecological photomedicine offers new diagnostic and therapeutic methods based on the interaction of light with the reproductive organs. One example is photodynamic therapy (PDT) in which photosensitizers are applied systemically or topically for selective endometrial ablation. Several studies describing the potential use of PDT for this application are reviewed. Basic experimental and clinical aspects of PDT, such as photosensitizer types, application modes, irradiation parameters, optical properties of tissues and photodegradation of photosensitizers are discusse

Optical Properties of Human Uterus at 630 nm

The optical properties of normal and fibriotic human uteri were determined using frequency-domain and steady-state techniques

Rat reproductive performance following photodynamic therapy with topically administered Photofrin

A rat animal model was used for comparing the photodynamic efficacy of two formulations of topically administered Photofrin in the uterus: 0.7 mg/kg Photofrin and 0.7 mg/kg Photofrin + 4% Azone, a penetrationenhancing agent. Uterine structure and reproductive performance were evaluated following illumination with 80 J/cm2 of 630 nm light. Fluorescence microscopy was employed to determine drug localization in frozen uterine sections at various times after drug administration. Functionality studies demonstrated a significant reduction in the number of implantations per treated uterine horn compared to controls. The mean number of implantations decreased systematically on increasing the interval between Photofrin administration and light application. At 72 h, 0.88 ± 0.52 gestational sacs per rat were recorded with Photofrin therapy, compared with 8.1 ± 1.12 (P = 0.01) on the untreated side, indicating nearly complete loss of reproductive capability. Similar results were achieved after only 3 h treatment with Photofrin + Azone (0.38 ± 0.26 sacs per rat versus 7.5 ± 1.07 on the untreated side; P = 0.01). This indicates that the effect of Photofrin can be enhanced either by extending the drug incubation period from 3 to 72 h or by adding the penetration-enhancing drug Azone. Fluorescence pharmacokinetic studies suggest that both forms of topically administered Photofrin are diffusely distributed throughout the endometrium at virtually the same rate. However, Azone may enhance the selectivity of photodynamic therapy by facilitating drug targeting to critical endometrial structure

Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring

ObjectiveThe 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.Study designThis 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.ResultsAfter 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.ConclusionOur 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