Biomedical Photonics (BMP - E-Journal)
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Интраоперационная флуоресцентная спектроскопия и фотодинамическая терапия при рецидивных опухолях малого таза на фоне местных лучевых повреждений
Get PDFThis work presents the results of performing intraoperative photodynamic therapy (IOPDT) on 22 patients with recurrent pelvic tumors(cervical cancer – in 18 patients, cancer of the corpus uteri – in 3 patients, cancer of the anal canal – in 1 patient). Prior to the PDT procedure, the patients were injected with photolon photosensitizer (PS) at a dose of 1.0–1.1 mg/kg. After the injection of PS, local fluorescence spectroscopy of tumor lesions was performed to determine the accumulation of drug in various areas of tumors and healthy tissue. Intraoperative laser irradiation was carried out 3–5 hours after the photolon injection with light at 662 nm wavelength using "Latus-2" laser device with a power density of 140 mW/cm2 and the density of light energy of 40–60 J/cm2, the number of irradiation fields was 3–5 depending on the anatomical features.The follow-up period after surgical treatment combined with PDT was from 6 to 24 months. Analyzing the immediate results of the treatment, there were no undesirable events or increase in the number of postoperative complications compared to patients treated without IOPDT. Were registered: transient increase in ALT and AST levels – in 5 patients (13.6%), reduction of oxygenation during anesthesia – in 20 (90.9%), transient fevers in the postoperative period – in 7 (31.8%).It was noted that IOPDT with photolon drug, while slightly extending the time of the operation, is well tolerated by patients and does not lead to an increase in the number of early postoperative complications or the length of hospitalization
Сравнительное экспериментальное исследование специфической активности 5-АЛК и гексилового эфира 5-АЛК
Get PDFA comparative experimental study of the specific activity of drugs based on 5-aminolevulinic acid (5-ALA) and its hexyl ester (5-ALA HE) was carried out. Their ability to induce the synthesis of photoactive protoporphyrin IX in the healthy tissues of the rabbit bladder when instilling the drug solutions at various concentrations has been estimated. It was shown that 5-ALA HE results in the induction and accumulation of PPIX in the rabbit bladder epithelium at much lower concentrations than 5-ALA. Thus, a significant increase in the fluorescence intensity in comparison with the control was achieved by instillation of 5-ALA HE solution in the rabbit’ bladder at a concentration of only 0.0001% (fluorescence intensity 2.20±0.60 a.u.), and for 5-ALA – only when using a solution at a concentration of 0.3% (fluorescence intensity 2.60±1.02 a.u.).Проведено сравнительное экспериментальное исследование специфической активности препаратов на основе 5-аминолевулиновой кислоты (5-АЛК) и ее гексилового эфира (ГЭ 5-АЛК). Оценена их способность индуцировать синтез фотоактивного протопорфирина IX в здоровых тканях мочевого пузыря кролика при инстилляции растворов препаратов в различных концентрациях. Исследования показали, что ГЭ 5-АЛК вызывает индукцию и накопление ППIX в эпителии мочевого пузыря кролика в значительно меньших концентрациях, чем 5-АЛК. Так, достоверное увеличение интенсивности флуоресценции по сравнению с контролем удалось достичь при инстилляции в мочевой пузырь кролика раствора ГЭ 5-АЛК в концентрации всего 0,0001% (интенсивность флуоресценции 2,20±0,60 усл.ед.), а для 5-АЛК – только при использовании раствора в концентрации 0,3% (интенсивность флуоресценции 2,60±1,02 усл.ед.)
ИССЛЕДОВАНИЕ ВНУТРИКЛЕТОЧНОГО РАСПРЕДЕЛЕНИЯ КРИСТАЛЛИЧЕСКИХ НАНОЧАСТИЦ МЕЗО-ТЕТРА(3-ПИРИДИЛ)БАКТЕРИОХЛОРИНА
Get PDFThe results of the study of subcellular distribution of molecular meso-tetra(3-pyridyl)bacteriochlorin nanocrystals proposed as therapeutic agents for photodynamic therapy are represented in the article. Investigations and measurement of spectroscopic properties of molecular crystals of near-infrared photosensitizer were conducted using special device complex based on fiber-optic spectrometer. Investigation and analysis of the pattern of subcellular accumulation of meso-tetra(3-pyridyl)bacteriochlorin in molecular (dimethyl sulfoxide (DMSO) as solvent) and nanocrystalline forms on different cell lines: human monocytes (THP-1), human cervical cancer cells (HeLa) and mouse malignant brain tumor cells (glioma C6). The dynamics of subcellylar accumulation of the agent at concentration of 5 and 10 mg/l was assessed with laser microscope-spectrum analyzer and by confocal microscopy. The study showed that in the course of interaction with cell lines molecular nanocrystals of the agent developed ability to fluorescence. Hence, in the cellular environment meso-tetra(3-pyridyl) bacteriochlorin nanoparticles became phototoxic giving opportunities for their use for fluorescence diagnosis and photodynamic therapy. Specific role of meso-tetra(3-pyridyl)bacteriochlorin in the range of photosensitizers is determined by its spectral characteristics, i.e. absorption and fluorescence in near-infrared band, which allows measuring and affecting on deeper layers of biotissue. Thus, the use of meso-tetra(3-pyridyl)bacteriochlorin nanoparticles as nanophotosensitizers may improve the efficacy of diagnosis and treatment of deep-seated tumors
ЭКСПЕРИМЕНТАЛЬНОЕ ОБОСНОВАНИЕ ВЫБОРА РЕЖИМОВ ОБЛУЧЕНИЯ ДЛЯ ИНТРАПЕРИТОНЕАЛЬНОЙ ФОТОДИНАМИЧЕСКОЙ ТЕРАПИИ С ФОТОСЕНСИБИЛИЗАТОРАМИ НА ОСНОВЕ ПОРФИРИНОВ И ФТАЛОЦИАНИНОВ
Get PDFOptimized 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
ФЛУОРЕСЦЕНТНАЯ ДИАГНОСТИКА И ФОТОДИНАМИЧЕСКАЯ ТЕРАПИЯ В КОМБИНИРОВАННОМ ЛЕЧЕНИИ ХОЛАНГИОЦЕЛЛЮЛЯРНОГО РАКА
Get PDFThe results of the pilot study of combined treatment for non-resectable cholangiocarcinoma complicated with obstructive jaundice are represented this paper. Method included percutaneous transhepatic biliary drainage, endoscopic fluorescence diagnosis, photodynamic therapy of tumor stricture, and stenting of bile ducts. Fourteen patients who underwent the treatment in the surgery department clinic of I.M. Sechenov First Moscow State Medical University were enrolled in the study. Fluorescence diagnosis and photodynamic therapy were carried out using photosensitizers photosens (0.5 mg/kg), fotolon (1 mg/kg), and radachlorin (1 mg/kg). The average light dose for one session was 115±5 J/cm2. Fluorescence diagnosis using endoscopic video-fluorescence system for endoscopy and minimally invasive surgery allowed to obtain videoassisted fluorescence image of the tumor and to measure level of photosensitizer fluorescence in tumor in all patients. Malignant tumor was confirmed by morphological study in 12 patients, biopsy of material for morphological study failed in 2 patients with Klatskin tumor. The preliminary results of combined minimally invasive treatment were assessed as promising. The survival time in 4 patients after treatment accounted for 21, 17, 13 and 11 months, respectively. For now 5 patients are under follow-up. Follow-up periods are 13 and 19 months in 2 of them and from 4 to 6 months in 3 of them. Five patients with multiple distant metastases before the treatment died in 3±1 months after therapy. The average lifetime in the treatment group is 9.5 months up to date, however the duration is expected to belonger because 5 of 14 patients are alive
ЗНАЧЕНИЕ РЕГИСТРАЦИИ ВЫЦВЕТАНИЯ ФОТОСЕНСИБИЛИЗАТОРА ДЛЯ ОЦЕНКИ МЕХАНИЗМА ДЕЙСТВИЯ ПРЕПАРАТОВ НА ФОТОИНДУЦИРОВАННЫЙ ГЕМОЛИЗ
Get PDFThe 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
ЦИТОРЕДУКТИВНОЕ ХИРУРГИЧЕСКОЕ ЛЕЧЕНИЕ С ИНТРАОПЕРАЦИОННОЙ ФОТОДИНАМИЧЕСКОЙ ТЕРАПИЕЙ БОЛЬНОЙ С МУЦИНОЗНЫМ КАНЦЕРОМАТОЗОМ БРЮШИНЫ
Get PDFClinical 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.Приведено клиническое наблюдение за пациенткой с орфанным заболеванием – муцинозным канцероматозом брюшины – после проведения 2 курсов интраоперационной фотодинамической терапии с фотосенсибилизатором фотогем. При проведении первого курса фотодинамической терапии фотогем вводили в дозе 2,5 мг/кг, плотность энергии лазерного излучения составила 10 Дж/см2. Продолжительность стабилизации после первого курса лечения – 2 года, после чего зарегистрировано прогрессирование заболевания. Второй курс фотодинамической терапии проводили в том же режиме. Продолжительность стабилизации после второго курса лечения – 2,5 года. Пациентка погибла в результате несчастного случая, не связанного с заболеванием
Пресс-релиз III зимней школы. Тема 2017: «Фотодинамическая терапия в онкодерматологии, дерматологии и косметологии»
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ИССЛЕДОВАНИЕ РАСПРЕДЕЛЕНИЯ ХЛОРИНОВЫХ ФОТОСЕНСИБИЛИЗАТОРОВ В ДВУХМЕРНЫХ И ТРЕХМЕРНЫХ КЛЕТОЧНЫХ КУЛЬТУРАХ
Get PDFThe aim of this study was to analyze the distribution of chlorin type photosensitizers (PS): chlorin e6 (Ce6) and dimethyl ester of chlorin e6 (DME), in human adenocarcinoma HT29 monolayer and multicellular spheroid cell cultures. There is an assumption, that the chemical modification of Ce6 molecules causes a change of intracellular location and the enhanced photosensitizing activity. Indeed, photodynamic therapy on monolayer cell culture with DME showed two times higher photokilling ability comparing with that of non-modified analogue.Ce6 and DME biodistribution processes in tumor tissue were studied on multicellular tumor spheroids model. Total amount of DME in multicellular tumor spheroids exceeded 1,3 times accumulation of Ce6. According to fluorescence microscopy studies, Ce6 and DME distribution patterns in the spheroids bulk were similar. Application of 2D and 3D tumor models for the analysis of photosensitizer distribution may allow predicting the photosensitizer biodistribution features for photodynamic therapy in vivo