Abstract Results of application of a new technology of intraoperative photodynamic therapy (IOFDT) in patients with peritoneal mesothelioma developed at P. Herzen Moscow Oncology Research Institute are presented. The study included 8 patients. 3 patients underwent surgery in various amount: 1 – limited peritonectomy in the volume of tumor foci resection and resection of a large omentum, 1 – limited peritonectomy in the volume of tumor foci resection and atypical resection of the right lobe of the liver, 1 – only resection of the large omentum due to the fact that the tumor was located only in a large omentum and no signs of lesions of the parietal peritoneum was revealed by intraoperative revision. Surgical intervention in these patients was concluded by IOPDT. The remaining 5 patients underwent only IOPDT. After the treatment, two patients underwent additional courses of laparoscopic IOPDT. Of the 8 patients enrolled in the study, 4 died from the underlying disease, 1 from cardiovascular disease with recurrence of the disease, 1 from cardiovascular disease without signs of recurrence, 2 were monitored for 6 months and 146 months (12 years). Thus, in the group of patients with peritoneal mesothelioma, the maximum observation period was 146.44 months, the median survival was 48.4 months, the total specific 1-year survival was 85.7±13.2%, the three-year survival was 68.5±18.6%, the 5-year survival was 45.7 ± 22.4 %. The average life expectancy after treatment of patients with repeated courses of laparoscopic IOPDT was 87 months, without repeated courses – 35.8 months. Thus, life expectancy was higher in patients with repeated courses of laparoscopic IOPDT. Small sample size caused to the rarity of this pathology does not allow for statistically significant conclusions. However, the results of the study indicate the prospects of multi-course intraoperative photodynamic therapy in patients with peritoneal mesothelioma.

The study of mean blood velocity changes in rat mesenteric venules (15–30 µm) due to photoactivation (λ = 532 nm, 0,175 W/cm2, 300 s) of i.v. injected Rose Bengal (17 mg/kg) is represented in the article. Using in vivo biomicroscopy the progressive decrease of mean blood velocity both during the laser irradiation and after it was registered. The calculation of thermal effects in the irradiated part of microvessel due to laser absorption by hemoglobin and Rose Bengal showed the rise of temperature was not exceed 0.2оC as compared to initial level. Thus, thermal effect has nearly no significant influence on microvascular disturbances caused by Rose Bengal photoactivation.

Cationic bacteriochlorins are promising as antibacterial photosensitizers (PS) for antibacterial photodynamic therapy. Current work is devoted to the study of properties of new nanostructured cationic photosensitizer based on cyclodextrin dispersion of bacteriochlorine derivative – 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester, for optimization of dispersion composition and selection of time interval between administration of the PS and photodynamic ttherapy of infected septic wounds. Specifics of absorption and fluorescence of PS in dependence of its concentration and proportions of components in dispersion was assessed. Pharmacokinetics and biodistribution of PS were studies in vivo in organs and tissues of intact mice and septic wounds infected with P. аeruginosa or S. aureus. The preliminary studies have shown high efficiency of antimicrobial photodynamic therapy of septic wounds with cyclodextrin dispersion of 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester. Results of study of absorption and spectral and fluorescence properties of its drug formulation depending on its composition allowed to recommend the use of weight ratio 133-N-(N-methylnicotinyl)bacteriopurpurinimide methyl ester : cyclodextrin about 1:200 and addition of 0,1% Tween 80 to reduce aggregation. The study showed that 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester was rapidly cleared from mouse blood circulation: more than 70% – for 2 h, 95% – for 1 day, more than 99% – for 6 days. About 98% was cleared from skin and muscles for 6 days. The long-term (up to 24 h) persistence of PS were observed in liver and kidneys, however more than 99% was cleared for 6 days. Thus, it may be supposed that elimination of PS form mice body is through kidneys and liver. After 24 h partial PS aggregation in tissues, particularly in skin and muscles, was observed. Thus, it may be supposed that the reduce of fluorescence intensity after 24 hand later was associated not only with its elimination from body but with its aggregation. Spectral and fluorescence studies showed that 133-N-(Nmethylnicotinyl)-bacteriopurpurinimide methyl ester selectively accumulated in septic wounds, fluorescence contrast was in the range of 3–4. The highest values of concentration and selectivity of its accumulation were achieved at 1.5–3 h after intravenous injection. The irradiation 2 h after injection provided high efficacy of the therapy of septic wounds.

The influence of three pharmaceutical preparations on photo-induced lysis (irradiation with light-emitting diode of 653 nm) of human erythrocytes in the presence of photosensitizer radachlorin and also on the quantum yield of radachlorin photobleaching was studied. Both processes are mediated by singlet oxygen generation and therefore can become a target for antioxidant or prooxidant regulation. The pyridine preparation mexidol (action principle – 3-hydroxy-6-methyl-2-ethylpyridine succinate) in concentration of 152 µM used as an antioxidant and a membrane protector and aminazine (action principle – chlorpromazine) in concentration of 70 µM many times accelerated manyfold the photo-induced hemolysis. However only mexidol increased the quantum yield of radachlorin photobleaching in many times. The obtained data showed the direct prooxidant action of mexidol, but not aminazine that accelerated a photo-induced hemolysis due to other mechanism. A pyridine preparation nicotinic acid tested in equimolar to mexidol concentration, failed to influence both the velocity of the photo-induced hemolysis and the quantum yield of radachlorin photobleaching. Our study shows the possible use of a photobleaching tests for detection of the direct prooxidant action.

The method of DNA-electrophoresis was used to study apoptosis in the lymph nodes of the abdominal lymphodissection zone after local intraoperative photodynamic therapy (PDT) for the gastrointestinal cancers. Apoptosis (apoptotic ladder) was determined in the four cell populations of lymph nodes:

– in the lymph nodes with metastases that have not been irradiated;

– in the irradiated during PDT lymph nodes with metastases;

– in the lymph nodes without metastases that have not been irradiated;

– in the irradiated during PDT lymph nodes without metastases.

The implementation of this study was possible due to intraoperative division of lymph nodes into two parts, one of which was removed while another one intentionally wasn’t removed and was irradiated (in human). It was also removed 60-90 minutes after PDT treatment and examined for apoptosis. As a result, it was found that apoptosis is detected in the irradiated during PDT lymph nodes with metastases. The obtained results show the fact that in the lymph nodes of the abdominal lymphodissection zone tumor cells selectively die by apoptosis as a result of the local intraoperative photodynamic therapy (PDT) for the gastrointestinal cancers while in non-malignant cells apoptosis doesn’t occur after PDT (p <0.01). Thus, the obtained clinical and experimental data made it possible to evaluate the target PDT effect and confirm the safety of the photodynamic effect on healthy tissues of the lymphoid system located in the irradiation zone.

A case of successful photodynamic therapy of residual laryngeal tumor after external beam radiotherapy (EBRT) is reported. The female patient with diagnosis of laryngeal cancer T1N0M0 underwent a course of EBRT on larynx, fraction dose = 2 Gy, 5 fractions per week, total radiation dose = 60 Gy. One month after EBRT the continued growth of residual tumor in the left vocal fold was diagnosed. The patient had 4 courses of photodynamic therapy with photosensitizer fotoditazin at a dose of 100 mg combined with electroresection of residual laryngeal tumor. The control video-assisted laryngoscopy 1 month after the 4th course of photodynamic therapy showed that larynx was flexible, vocal function was fully restored, tumor of the left vocal fold wasn’t detected. Non-recurrence follow-up period is 10 month. The patient is under follow-up.

Clinical observation of a patient with an orphan disease (mucinous peritoneal carcinomatosis) after 2 courses of intraoperative photodynamic therapy with photogem photosensitizer is presented. During the first course of photodynamic therapy, photogem was administered at a dose of 2.5 mg/kg, the energy density of the laser radiation was 10 J/cm2. The duration of stabilization after the first course of treatment was 2 years, after which the progression of the disease was registered. The second course of photodynamic therapy was carried out in the same way. The duration of stabilization after the first course of treatment was 2.5 years. The patient died as a result of an accident unrelated to the disease.