Biomedical Photonics (BMP - E-Journal)
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    Интраоперационная флюоресцентная диагностика у больных с метастатическим поражением головного мозга

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    The technique of intraoperative fluorescence diagnosis with alasens for brain metastases includes visual assessment of alasens-induced protoporphyrin IX fluorescence and local spectroscopy. The technique allows to reduce the rate of misdiagnosis, to assess accurate local extent of brain metastases and to improve surgical radicality. When applying this technique the sensitivity of fluorescence diagnosis is 96.7%, the specificity is 100%. The technique is designed for neurosurgeons specialized on neurooncology. Технология интраоперационной флюоресцентной диагностики с препаратом аласенс метастатического поражения головного мозга включает визуальную оценку флюоресценции аласенс-индуцированного протопорфирина IX и локальную флюоресцентную спектроскопию. Технология позволяет снизить число диагностических ошибок, достоверно оценить местную распространенность внутримозговых метастазов и повысить радикальность оперативного вмешательства. При применении данной технологии чувствительность флюоресцентной диагностики составляет 96,7%, специфичность 100%. Технология предназначена для врачей- нейрохирургов, занимающихся проблемами нейроонкологии.

    Фотодинамическая терапия: развитие метода и применение в клинической практике ФГБУ МРНЦ МЗ РФ

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    This article is dedicated to clinical experience of photodynamic therapy (PDT) in Medical Radiological Research Center. Authors represent the results of treatment in 156 patients with primary untreated tumors of different localizations as follows: basal cell skin cancer (BCSC) in 156 patients, squamous cell carcinoma of the skin (SCCS) in 24 patients, cancer of upper and lower lips in 30 patients. The other group of patients included recurrent and metastatic diseases: recurrent BCSC were in 127 patients, recurrent or continued growth of SCCS – in 27, recurrent or continued growth of lip cancer – in 13, intracutaneous metastases of skin melanoma (62 patients) and breast cancer (46) – in 108. PDT was performed with photosensitizers Photosense (2.0 mg/kg), Photolon (0.9–2.5 mg/kg), and Photoditazine (0.7–0.8 mg/kg). The light irradiation dose was 100–600 J/cm2. After PDT of previously untreated BCSC the complete regression (CR) of tumor lesions was in 96.8% of patients, partial regression (PR) – in 3.2% of patients; for PDT of recurrent BCSC in 76.4% and 23.6%, respectively. After PDT treatment in patients with previously untreated SCCS CR of tumor lesions was achieved in 91.7% of patients, PR – in 8.3% of patients. For treatment of relapses in SCCS CR was achieved in 59.3% of cases, PR – in 33.3%, absence of regression was reported in 7.4% of cases. PDT of intracutaneous metastases of skin melanoma and breast cancer provided positive treatment effect (CR + PR + stabilizing) in 95 and 98% of cases, respectively. CR in primary lip cancer after PDT was reported in 86.0% of patients, PR – in 14.0%. For PDT of recurrent lip cancer CR accounted for 69.2%, PR – 30.8%.

    Фотодинамическая терапия ангиосаркомы мягких тканей волосистой части головы как альтернатива хирургическому лечению у больного с тяжелой сопуствующей патологией

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    A case of successful photodynamic therapy in patient of 86 y.o. with diagnosis: angiosarcoma of right temporal-parietal region stage IIA (Т2вN0M0) is reported. The tumor was as soft tissue round shape lesion with tuberous contours 3.4х3.4х1.1 cm in size, located in subcutaneous tissue in right parietal region with no scull bone invasion. The patient was refused to surgical treatment with general anesthesia due to severe cardiovascular co-morbidity. The patient underwent a course of photodynamic therapy with Photolon. The photosensitizer was intravenousely introduced for 3 h before irradiation at dose of 1 mg/kg body weight. The parameters of irradiation were as follows: output power – 0.8 W, light dose – 150 J/cm2, 4 irradiation fields 2.5 cm in diameter. During the irradiation there were moderate pain which did not require drug management. After PDT complete regression of the tumor was achieved. For nowadays (11 months after treatment) the patient is observed with no recurrence. The reported case shows that photodynamic therapy may be successfully used for alternative treatment of soft tissue angiosarcoma in patients with no ability for surgical treatment.

    Флюоресцентная диагностика и фотодинамическая терапия – обоснование применения и возможности в онкологии

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    This article is dedicated to current research of domestic photosensitizers of different classes carried out by Hertzen Moscow Cancer Research Institute. Results of research in tissue distribution kinetics of Photogem, Photosense, Chlorine e6 based photosensitizers and 5-ALA induced protoporphyrine IX (PPIX) in cancer patients are represented. These results have been used for development of medical techniques in fluorescence diagnostics (FD) and photodynamic therapy (PDT). This article summarizes Hertzen Moscow Cancer Research Institute results of 20 years experience of PD and PDT in patients with different cancer diseases. The most recent data on the efficacy of radical and palliative PDT, anti-relapse intra-operative PDT, prolonged PDT, and PDT combined with chemotherapy are given. Data on sensitivity and specificity of FD in patients with different tumor localizations are represented. The author outlines achievements and challenges of novel FD and PDT methods in clinical practice and defines the main directions of the further FD and PDT development.Статья посвящена исследованиям отечественных фотосенсибилизаторов различных классов, проводимых в МНИОИ им. П.А. Герцена. Приведены результаты изучения кинетики тканевого и внутритканевого распределения препаратов фотогем, фотосенс, препаратов на основе хлорина е6 и аласенс-индуцированного протопорфирина IX (ППIX) у онкологических больных, послужившие основой для разработки медицинских технологий флюоресцентной диагностики (ФД) и фотодинамической терапии (ФДТ). В статье обобщены результаты 20-летнего применения в МНИОИ им. П.А. Герцена ФД и ФДТ у пациентов с различными онкологическими заболеваниями. Приведены последние данные по эффективности радикальной и паллиативной ФДТ, интраоперационной противорецидивной ФДТ, пролонгированной ФДТ, а также сочетанной с химиотерапией ФДТ. Представлены данные по специфичности и чувствительности ФД у пациентов с опухолями различной локализации. Автором отмечены достижения и существующие проблемы применения современных методов ФД и ФДТ в клинической практике, намечены основные направления их дальнейшего развития.

    Возможности мультиспектральной аутофлюоресцентной визуализации злокачественных опухолей

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    The applications of multispectral autofluorescence imaging of malignant tumor was shown in in vitro and in vivo experiments. Using ТС-1 mouse tumor model it was demonstrated that the location of tumor formation can be clearly identified as early as 2 days after injection of tumor cells. Among observed effects the new one is an unusually active angiogenesis at early stage of tumor formation accompanied by atypical tortuous vessels with growth rate up to 3 mm/day. Two-wave excitation simultaneous laser with excitation on wavelength of 390 nm and 635 nm is shown to be promising for autofluorescence diagnosis along with single-wave excitation which is conventionally performed in the violet-blue region of the spectrum. This mode of excitation allows detecting the increased level of protoporphyrin IX even at early stage of carcinogenesis. The fluorescence due to active synthesis of protoporphyrin IX was shown to correlate with density of vessels. Increase of this fluorescence is observed also for aseptic inflammation but it has diffuse pattern which allows differentiating it from local fluorescence image at the site of tumor formation. The possibility of successful achievement of high-quality image using multispectral imaging and also optimization of registration settings were demonstrated in the experiment. The study of surgical specimen showed capabilities of imaging and measurement of autofluorescence in tumor tissue. The obtained results are intended to help in the development of endoscopic methods of imaging and devices for diagnosis of early tumors.

    Длительное паллиативное лечение больной перстневидно-клеточным раком желудка с использованием эндоскопической фотодинамической терапии

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    A case of multiple course of photodynamic therapy (PDT) in patient with gastric cancer T1N0M0. Morpholological diagnosis in this patient was signet ring cell cancer. For 8 years the patient underwent endoscopic organ-sparing treatment: PDT with Photohem (17 courses), electrocoagulation of tumor (3 sessions). The drug Photohem was introduced intravenously at dose of 3.0 mg/kg body weight for 48 h before PDT. The treatment result was only partial regression of gastric tumor, the maximal follow-up period with no endoscopic and morphological signs of tumor growth accounted for 8 months. However besides incomplete removal of gastric tumor and morphological type, for check-up examination 8 years after the onset of endoscopic treatment there were no features of regional and distant metastases according to chest and abdominal CT and US. Описан клинический случай применения многокурсовой фотодинамической терапии (ФДТ) для лечения больной раком желудка стадии T1N0M0. Морфологически у пациентки диагностирован перстневидно-клеточный рак. Пациентке на протяжении 8 лет выполнялось эндоскопическое органосохраняющее лечение: ФДТ с препаратом фотогем (17 курсов), электрокоагуляция опу- холи (3 сеанса). Препарат фотогем вводили внутривенно в дозе 3,0 мг/кг массы тела за 48 ч до проведения ФДТ. В результате проведенного лечения была достигнута лишь частичная регрессия опухоли желудка, максимальный срок наблюдения без эндоскопических и морфологических признаков опухолевого роста составил 8 мес. Однако, несмотря на неполное удаление опухоли желудка и ее морфологическую форму, при контрольном обследовании через 8 лет от начала эндоскопического лечения у больной, по данным КТ и УЗИ органов брюшной и грудной полостей, не было выявлено признаков регионарного и отдаленного метастазирования.

    Интраоперационная флюоресцентная диагностика при удалении эпендимомы шейно-грудного отдела позвоночника

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    The case of successful intraoperative fluorescence diagnosis (IOFD) for removal of cervical and thoracic ependymoma performed in P.A. Herzen MCRI is reported. For FD we used the Alasens (Research Institute of Organic Semi-Finished Products and Dyes). The drug solution was given per os at a dose of 20 mg/kg body weight 2.5 h before surgery. IOFD was per-formed 3 h after intake of photosensitizer. For fluorescence diagnosis there was average in-tensity of fluorescence in tumor and no fluorescence in normal spinal tissues. The extent of surgery was determined according to results of IOFD. The control MRI of cervical and supeior thoracic spine with contrast enhancement and follow-up confirmed definitive removal of tumor and showed no postoperative complications.Описан клинический случай успешного проведения интраоперационной флюоресцентной диагностики (ИОФД) при хирургическом удалении эпендимомы шейно-грудного отдела позвоночника в МНИОИ им. П.А. Герцена. Для выполнения ИОФД применяли препарат аласенс (ФГУП «ГНЦ «НИОПИК»). Пациент принимал внутрь раствор препарата в дозе 20 мг/кг массы тела за 2,5 ч до начала операции. Диагностика была проведена через 3,0 ч после приема аласенса. При флюоресцентной диагностике была отмечена флюоресцен- ция опухоли и отсутствие флюоресценции неизмененных тканей спинного мозга. Объем хирургического вмешательства определен с учетом данных ИОФД. По результатам контрольной МРТ шейного и верхнегрудного отдела позвоночника с контрастным усилением и динамического наблюдения за пациентом подтверждена радикальность удаления опухоли и отсутствие осложнений после проведен- ного лечения.

    Аппаратурное и инструментальное обеспечение флюоресцентной диагностики и фотодинамической терапии

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    The results of hardware and tool development in photodynamic therapy and fluorescence diagnostics performed by the Natural Research Center, A.M. Prokhorov General Physics Institute, Russian Academy of Sciences in collaboration with several research and medical institutes are presented. Physical and technical aspects of the problem are mentioned. We describe schemes and the principle of operation of devices which we use with our medical colleagues in clinical and experimental studies. Some results of clinical use of the developed devices and methods are presented. Представлены результаты аппаратных и инструментальных разработок в области фотодинамической терапии и флюоресцентной диагностики, проведенных Центром естественно-научных исследований Института общей физики им. А.М. Прохорова Российской академии наук совместно с другими исследовательскими и медицинскими институтами. Приведены схемы и описаны принципы работы устройств, используемых в клинических и экспериментальных исследованиях. Представлены некоторые результаты использования разработанных устройств в клинической практике.

    Фотодинамическая активность производного тетраазахлорина в экспериментах in vivo

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    The results of investigation for photodynamic activity of new tetraazachlorin derivate – tetramethyltribenzotetraazachlorin, synthesized in Research Institute of Organic Intermediates and Dyes. The study was performed on female mice of СВА line. The tumor model was transferred solid ascetic sarcoma S-37. The samples of photosensitizer, previously solubilized in 10% aqueou s solution ofCremophor EL, injected to mice intravenously on the 7th day of tumor growth in dose of 1–2 mg/kg. Two hours later the irradiation of sensitized tumor using light emitting diode device in a maximal wavelength of 755 nm (light power density – 50 mW/cm2, maximal total light dose – 300 J/cm2) was performed. The efficacy of photodynamic therapy was assessed by growth inhibition rates in the study group comparing with control group. The study showed that photodynamic therapy with investigated sample in dose of 2 mg/kg and light dose of 300 J/cm2 significantly inhibited the tumor growth (inhibition rate of 70–80% within 20 days), indicating prospectivity of subsequent investigations of tetraazachlorin as photosensitizer for photodynamic therapy of malignant tumors.

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