STUDY OBJECTIVE: To determine both the time leading to maximum endometrial drug uptake and distribution of the photosensitizer benzoporphyrin derivative-monoacid ring A (BPD-MA) after intrauterine instillation (Canadian Task Force classification ). DESIGN: Assessment of histology specimens (Canadian Task Force classification I). SETTING: University-based facility. PATIENTS: Twenty-two women scheduled for hysterectomy. INTERVENTIONS: We instilled 1.5 ml of a 2 mg/ml of BPD-MA-Hyskon solution into the uterine cavity of 22 women before hysterectomy. The fluorescence induced was measured by fluorescence microscopy on frozen sections of uterine samples from 20 of 22 patients. Systemic uptake of BPD-MA was determined in plasma of six patients by spectrofluorometry. MEASUREMENTS AND MAIN RESULTS: The BPD-MA-induced fluorescence was maximum 1 hour after instillation, with significantly higher uptake in endometrial glands than in underlying stroma. Hormonal endometrial stimulation correlated with fluorescence intensity: atrophy < secretory phase < proliferative phase. Strongest fluorescence was seen in endometrial cancer. Drug uptake by endometrial glands was found at a depth of 2 mm from the surface. Systemic uptake of BPD-MA was under the detection level of 2 ng/ml after application. CONCLUSION: Fluorescence in human endometrial glands suggests that selective destruction of human endometrium with photodynamic therapy may be possible 1 hour after topical application of BPD-MA for benign and malignant lesions. No systemic drug uptake, side effects, or major technical difficulties were detected. Limited penetration of the drug and selective uptake by endometrial glands provided a high degree of safety for endometrial ablation.
STUDY OBJECTIVE: To determine both the time leading to maximum endometrial drug uptake and distribution of the photosensitizer benzoporphyrin derivative-monoacid ring A (BPD-MA) after intrauterine instillation (Canadian Task Force classification ). DESIGN: Assessment of histology specimens (Canadian Task Force classification I). SETTING: University-based facility. PATIENTS: Twenty-two women scheduled for hysterectomy. INTERVENTIONS: We instilled 1.5 ml of a 2 mg/ml of BPD-MA-Hyskon solution into the uterine cavity of 22 women before hysterectomy. The fluorescence induced was measured by fluorescence microscopy on frozen sections of uterine samples from 20 of 22 patients. Systemic uptake of BPD-MA was determined in plasma of six patients by spectrofluorometry. MEASUREMENTS AND MAIN RESULTS: The BPD-MA-induced fluorescence was maximum 1 hour after instillation, with significantly higher uptake in endometrial glands than in underlying stroma. Hormonal endometrial stimulation correlated with fluorescence intensity: atrophy < secretory phase < proliferative phase. Strongest fluorescence was seen in endometrial cancer. Drug uptake by endometrial glands was found at a depth of 2 mm from the surface. Systemic uptake of BPD-MA was under the detection level of 2 ng/ml after application. CONCLUSION: Fluorescence in human endometrial glands suggests that selective destruction of human endometrium with photodynamic therapy may be possible 1 hour after topical application of BPD-MA for benign and malignant lesions. No systemic drug uptake, side effects, or major technical difficulties were detected. Limited penetration of the drug and selective uptake by endometrial glands provided a high degree of safety for endometrial ablation.
Authors: Gabriela Correia-Barros; Beatriz Serambeque; Maria João Carvalho; Carlos Miguel Marto; Marta Pineiro; Teresa M V D Pinho E Melo; Maria Filomena Botelho; Mafalda Laranjo Journal: Bioengineering (Basel) Date: 2022-05-23