Search

Optimized irradiation regimens for intraperitoneal photodynamic therapy with porphyrin and phthalocyanine photosensitizers are determined in in vitro and in vivo studies.The experimental study on НЕр2 cell line showed that reduce of power density for constant light dose increased significantly the efficacy of photodynamic therapy (the reduce of power density from 20-80 mW/cm2 to 10 mW/cm2 had the same results (90% cell death) for half as much concentration of the photosensitizer).The obtained results were confirmed in vivo in mice with grafted tumor S-37. For light dose of 90 J/cm2 and power density of 25 mW/cm2 none of animals in the experimental group had total resorption of the tumor. For the same light dose and decrease of power density to 12 mW/cm2 total tumor resorption was achieved in 34% of animals, 66% of animals died from phototoxic shock. For twofold decrease of light dose – to 45 J/cm2 with the same low-intensity power density (12 mW/cm2) we managed total tumor resorption in 100% of animals.In the following studies of optimized irradiation regimen for intrapleural photodynamic therapy the reaction of intact peritoneum of rats on photodynamic exposure was assessed and optimized parameters of laser irradiation, which did not cause necrosis and intense inflammatory reaction of peritoneum, were determined – light dose of 10 J/cm2 with power density of mW/cm2.Thus, the reasonability for use of low-intensity regimens of irradiation for intraperitoneal photodynamic therapy was confirmed experimentally with possibility of high efficacy of treatment without inflammatory reactions of peritoneum.

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.

The main stages of development and establishment of photodynamic therapy (PDT) in Russia are described in the article. Brief description of photosensitizers approved for clinical use in Russia including fotogem, photosens, alasens, radachlorine and fotoditazin is represented. Their physical and chemical and spectral characteristics, drug formulations, results of pre-clinical studies and post-marketing experience are shown. Main research centers dealing with PDT are listed.