Pilot studies of pharmacokinetics and pharmacodynamics of new photosensitizer liposomal boronated chlorine in mice with melanoma В16 were performed. Dynamics of drug accumulation in tumor and normal tissue (level of accumulation in tissues was assessed by means of fl uorescence) was studied. For intraperitoneal injection at a dose of 5 mg/kg the drug was shown to accumulate gradually in tumor and normal tissues with maximal fl uorescence values in 2–3 h after injection. Then fl uorescence intensity in tissues gradually decreased, achieving nearly initial base-line in 120 h after beginning of the study. The hotosensitizer accumulated in tumor tissue with average selectivity: contrast index for maximal drug accumulation in tissues accounted for 1.7–2.8. According to obtained data for following research the time interval between drug injection and irradiation of 3h was chosen. On the second stage of the study dependence of photodynamic therapy effi cacy on different parameters including photosensitizer dose for intraperitoneal injection (5–10 mg/kg), light dose (150–300 J/cm²) and power density (0.25–0.51 mW/cm²). The irradiation was performed by semiconductor laser on wavelength of 662±1 nm. The effi cacy was maximal for following regimen: photosensitizer dose of 5 mg/kg, light dose of 300 J/cm², power intensity of 0.44 mW/cm². For this regimen at the end of follow-up (21 days) complete tumor regression was obtained in 75% of animals and average coeffi cient of absolute tumor growth accounted for only 7.82.

Current views on mechanisms of therapeutic effect of photodynamic therapy for treating of cancer patients are represented. The history of formation and development of the method is described. The main requirements for agents used as photosensitizers are listed. Detailed review of main photosensitizers used in clinical practice in Russia and in foreign countries with their chemical structure, main spectral characteristics was performed. Methods of its application, therapeutic dose ranges, indications, specifi c pharmacokinetic properties and side-effects are briefl y outlined. Advantages and disadvantages of the most popular modern photosensitizers, main mechanisms of entry of photosensitizers of different chemical structure into cancer cells are observed. Three main possible component of anti-tumor effect: direct damage of cancer cells, impairment of vascular stroma of tumor and elimination of tumor due to immune cells are shown and closely discussed. Necrosis and apotosis of neovascular net which are main development trends of anti-tumor action for photodynamic therapy are noticed.

Comprehensive study for optimization of parameters of photodynamic action with fotoditazin in patients with tumor and pre-tumor cervical diseases was conducted. The study included 52 female patients: pre-invasive cervical diseases were diagnosed in 34 (CIN I – in 9, CIN II – in 13, CIN III – in 12), cervical cancer – in 11 (8 had squamous cell cancer, 3 – adenocarcinoma of cervical canal), chronic cervicitis – in 7. The study agent in the form of 0,5% gel was applied on cervix in dose of 1 ml. To detect optimal interval between gel application and conduction of photodynamic therapy dynamics of accumulation and elimination of photosensitizer by means of its fl uorescence was studied. Fotoditazin was shown to have good accumulation in pathological tissues. The maximal agent accumulation was noticed in 30 min, continued about 15 min, and then gradually decreased. Maximal fl uorescence of photosensitizer was observed in foci of malignant tumor and severe intraepithelial neoplasia. To detect optimal light dose for irradiation cytological study of cell smear from specimen after light exposure with different light doses was performed. The minimal light dose necessary for activation of photochemical reaction pathway was 100 J/cm², and optimal – 250 J/cm². This dose allowed to destroy all atypical cells in the area of light exposure after application of gel fotoditazin. According to obtain data we suppose that the most effi cient regimen of photodynamic therapy with local application of fotoditazin-gel for treating dysplasia and pre-invasive cervical cancer was a dose of laser irradiation of 250 J/cm² with duration of application of 30–45 min.

Results of treating 114 skin metastases of melanoma in 21 patients are represented. Melanoma progression with cutaneous metastases after previous treatment was diagnosed in all patients. The method of prolonged photodynamic therapy developed by authors with fotosens administrated intravenously at dose of 0.4 mg/kg of body weight was used in the study. First session of tumor irradiation was performed 2 h after injection of photosensitizer. Patients underwent superfi cial or contact irradiation depending on topography and type of growth of metastatic foci. Course of treatment accounted for 7–10 sessions of photodynamic therapy with 24 h interval, light dose delivered to tumor for one session – 350 J/cm². Signifi cant clinical effect (complete and partial tumor regression) was obtained in 89% of cases for developed method.

Results of follow-up of patient with melanoma metastases to inguinal lymph nodes (two tumor foci) are represented. The patient underwent a course of combined photodynamic therapy and distant gamma-ray therapy. Single intravenous injection of fotosens as photosensitizer at dose of 0.3 mg/kg was administered to the patient. Distant gamma-ray therapy was performed daily during 12 days (single dose of 3 Gy, total dose of 36 Gy), beginning in a day after injection of photosensitizer. Two hours after gamma-ray therapy session contact photodynamic therapy on both metastatic tumors was performed. There were 7 sessions of photodynamic therapy in all, total light dose on each tumor accounted for 1800 J. Three weeks after combined modality treatment the second step of radiotherapy on inguinal region including 12 daily irradiation sessions (single dose of 3 Gy, total dose of 36 Gy) was performed. One year after treatment the patient had complete tumor resorption proved in 6 months. There were no additional treatment during this period in this patient. The patient is still under follow-up.