Nuclear Medicine in Breast Cancer Diagnostics: Primary Tumor and Lymphatic Metastasis

The purpose of the study: to assess the possibility of using nuclear medicine techniques at the stages of diagnosis and treatment of breast cancer. Materials and Methods: The study included 290 patients with breast cancer and 70 patients with benign breast tumors. The study was used as a radiopharmaceutical 99mTc-MIBI, 199Tl for imaging tumors and colloid 99mTc-Aloteh for visualization sentinel lymph nodes (SLN), colloid was injected peritumoral in four points to 80 MBq one day prior to the planned operation. Results: The sensitivity of SPECT using both 99mTc-MIBI and 199Tl for breast cancer detection was shown to be rather high, being 98.5% and 98%, respectively. It should be noted that the sensitivity of SPECT in detection of small tumors (less than 1 cm in diameter) and multicentric tumors was not high irrespective of the radioisotope used (60% and 65% with 99mTc-MIBI and 65% and 59% with 199Tl, respectively). The difference in the sensitivity was found between 99mTc-MIBI and 199T for the detection of regional lymph node metastasis (91% vs 70%). SLN were detected in 31 patients. The most commonly SLN were defined in the axillary region of 96.7%. In 22 (70.9%) patients there was no metastasis SLN. The sensitivity of the method was 91.2%, specificity of 100%. Conclusion: The specificity of SPECT with 199Tl was higher than that with 99mTc-MIBI. The data obtained show that SPECT with 199Tl can be recommended for its use as an additional breast cancer detection method in cases when other imaging techniques and histological findings are not accurate enough. The clinical study of 99mTc-Aloteh, a new radiopharmaceutical agent, has shown that the studied colloid has high uptake level in SLN and can be successfully used for visualization of SLN in patients with breast cancer

Nuclear Medicine in Breast Cancer Diagnostics: Primary Tumor and Lymphatic Metastasis

The purpose of the study: to assess the possibility of using nuclear medicine techniques at the stages of diagnosis and treatment of breast cancer. Materials and Methods: The study included 290 patients with breast cancer and 70 patients with benign breast tumors. The study was used as a radiopharmaceutical 99mTc-MIBI, 199Tl for imaging tumors and colloid 99mTc-Aloteh for visualization sentinel lymph nodes (SLN), colloid was injected peritumoral in four points to 80 MBq one day prior to the planned operation. Results: The sensitivity of SPECT using both 99mTc-MIBI and 199Tl for breast cancer detection was shown to be rather high, being 98.5% and 98%, respectively. It should be noted that the sensitivity of SPECT in detection of small tumors (less than 1 cm in diameter) and multicentric tumors was not high irrespective of the radioisotope used (60% and 65% with 99mTc-MIBI and 65% and 59% with 199Tl, respectively). The difference in the sensitivity was found between 99mTc-MIBI and 199T for the detection of regional lymph node metastasis (91% vs 70%). SLN were detected in 31 patients. The most commonly SLN were defined in the axillary region of 96.7%. In 22 (70.9%) patients there was no metastasis SLN. The sensitivity of the method was 91.2%, specificity of 100%. Conclusion: The specificity of SPECT with 199Tl was higher than that with 99mTc-MIBI. The data obtained show that SPECT with 199Tl can be recommended for its use as an additional breast cancer detection method in cases when other imaging techniques and histological findings are not accurate enough. The clinical study of 99mTc-Aloteh, a new radiopharmaceutical agent, has shown that the studied colloid has high uptake level in SLN and can be successfully used for visualization of SLN in patients with breast cancer

Clinical Significance of Sentinel Lymph Node Detection in Patients with Invasive Cervical Cancer

The clinical significance of determining sentinel lymph nodes (SLN) in patients with invasive cervical cancer was studied. From 2013 to 2014, 30 cervical cancer patients (T1a1NxM0-T1b1NxM0) were treated at the Gynecological Oncology Department of the Cancer Research Institute. The day before surgery, four submucosal injections of 99mTc Al2O3 at a total dose of 80 MBq were made in each quadrant around the cervical tumor. Patients were submitted to preoperative lymphoscintigraphy and intraoperative SLN detection. The feasibility of preserving the reproductive potential in patients after radical abdominal trachelectomy was assessed. The 3-year, overall, disease-free and metastasis-free survival rates were analyzed. Thirty-four SLNs were detected by single-photon emission computed tomography (SPECT) and 42 SLNs were identified by intraoperative gamma probe. The sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 80% for SPECT image. The reproductive potential was preserved in 86% of patients. The 3-year overall and metastases-free survival rates were 100%. Recurrence occurred in 8.6% of cases

Development and Study of {99m}Tc-1-Thio-D-glucose for Visualization of Malignant Tumors

The preclinical studies of {99m}Tc-1-Thio-D-glucose, a new tumor-seeking agent based on technetium-99mlabeled glucose derivative, were conducted, and the feasibility of using this radiopharmaceutical for tumor visualization was studied. The preclinical studies were carried out strictly in accordance with the local legislation and were regulated by the generally accepted research standards. {99m}Tc-1-Thio-D-glucose was found to have optimal pharmacokinetic and physico-chemical properties for diagnostic imaging and was proved to belong to the low-toxic substances. The potential utility of {99m}Tc-1-thio-D-glucose for tumor imaging was studied in vitro and in vivo models. The present study demonstrated that {99m}Tc-1-Thio-D-glucose is a prospective radiopharmaceutical for cancer visualization

Development and Study of {99m}Tc-1-Thio-D-glucose for Visualization of Malignant Tumors

The preclinical studies of {99m}Tc-1-Thio-D-glucose, a new tumor-seeking agent based on technetium-99mlabeled glucose derivative, were conducted, and the feasibility of using this radiopharmaceutical for tumor visualization was studied. The preclinical studies were carried out strictly in accordance with the local legislation and were regulated by the generally accepted research standards. {99m}Tc-1-Thio-D-glucose was found to have optimal pharmacokinetic and physico-chemical properties for diagnostic imaging and was proved to belong to the low-toxic substances. The potential utility of {99m}Tc-1-thio-D-glucose for tumor imaging was studied in vitro and in vivo models. The present study demonstrated that {99m}Tc-1-Thio-D-glucose is a prospective radiopharmaceutical for cancer visualization

ДИАГНОСТИЧЕСКИЕ РАДИОФАРМАЦЕВТИЧЕСКИЕ ПРЕПАРАТЫ НА ОСНОВЕ ПРОИЗВОДНЫХ ГЛЮКОЗЫ В СОВРЕМЕННОЙ ОНКОЛОГИЧЕСКОЙ ПРАКТИКЕ

The purpose of the study was to review available literature on the efficacy of radiopharmaceuticals based on glucose derivatives labeled with radioactive isotopes for detection of various cancers. Material and methods. A systematic literature review was performed using the Scopus, Web of Science, MedLine, Cochrane Library, EMBASE, and Global Health databases from 2000 to 2016. Out of 900 papers in the field of nuclear medicine, 58 were included into the review. Results. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) has been approved to be a powerful imaging tool for the detection of various cancers as well as for the assessment of tumor extent and therapy response. There is a continuous search for new more specific and effective radiopharmaceuticals for visualization of tumor tissue. Many studies are devoted to the development of radiopharmaceuticals based on technetium-99m labeled glucose derivatives for tumor visualization. Russian researches have made a significant progress in the development of imaging agents for single-photon emission computed tomography. Conclusion. Despite the widespread use of positron emission tomography technologies, which have proved to be effective, the specialists still have a great interest in radiopharmaceuticals based on technetium-99m. The literature review suggests that the emergence of a diagnostic radiopharmaceutical based on technetium-99m labeled glucose derivative will help to improve the availability of nuclear medicine methods and their effectiveness.Цель исследования – анализ имеющихся на сегодняшний день литературных данных об эффективности применения диагностических радиофармацевтических препаратов на основе меченных радиоактивными изотопами производных глюкозы в визуализации злокачественных новообразований различных локализаций. Материал и методы. Поиск соответствующих источников производился в системах Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health и РИНЦ, включались публикации с 2000 по 2016 г. Из 900 источников в обзор были включены 58 наиболее полных и фундаментальных трудов в области ядерной медицины. Результаты. В настоящее время в онкологии достаточно широко используется диагностический радиофармацевтический препарат на основе меченной фтором-18 производной глюкозы – 18F-дезоксиглюкоза (18F-ФДГ). Применение указанного радиофармпрепарата доказало свою эффективность в визуализации злокачественных новообразований различных локализаций, оценке распространенности опухолевого процесса и оценке эффективности проводимого лечения. При этом в мире идет поиск новых, более специфичных и эффективных радиофармпрепаратов для визуализации опухолевой ткани. Достаточно много трудов посвящено разработке радиофармацевтических препаратов на основе меченных технецием-99m производных глюкозы для визуализации опухолевой ткани. Значительных результатов в этой области достигли отечественные исследователи, разрабатывающие оригинальные препараты для однофотонной эмиссионной компьютерной томографии. Заключение. Несмотря на широкое распространение в мире технологий позитронно-эмиссионной томографии, доказавшей свою эффективность, у специалистов по- прежнему остается большой интерес к радиофармацевтическим препаратам на основе технеция-99m. Анализ литературы свидетельствует о том, что появление диагностического радиофармацевтического препарата на основе меченной технецием-99m производной глюкозы поможет повысить доступность методов ядерной медицины и их эффективность

Альтернативные каркасные белки в радионуклидной диагностике злокачественных образований

This review discusses a relatively new class of targeted molecules that is being actively studied for radionuclide diagnosis and treatment of malignancies. The full-size antibodies used so far have non-optimal pharmacological properties, slow distribution in the body, poor penetration into the tissue and kidney excretion, and high immunogenicity, which significantly complicates their use in clinical practice. Over the past decade, a new class of targeted molecules, called “non-immunoglobulin scaffolds” have become popular; they have all the requirements for optimal delivery of a radionuclide to tumor cells. Scaffolds usually are smaller in size in comparison with antibodies, but they are larger than peptides, and are characterized by high affinity and optimal biochemical, biophysical, biological, and economic features. The advantages of such proteins are their stable structure, good penetration into tissues, the possibility of additional functionalization and expression in the bacterial system, which ensures low production costs.The results of preclinical and clinical studies for diagnosis of malignancies using such proteins as affibody, adnectin, DARPins, etc., have demonstrated their high specificity, affinity, good tolerance and low immunogenicity. В настоящем обзоре обсуждается относительно новый класс направленных адресных молекул, активно исследующийся в отношении радионуклидной диагностики и лечения злокачественных образований. Используемые до настоящего времени полноразмерные антитела обладают неоптимальными фармакологическими свойствами, медленным распределением в организме, плохим проникновением в ткани, выведением почками и высокой иммуногенностью, что существенно затрудняет их применение в клинической практике. В течение последнего десятилетия большую популярность приобретают таргетные молекулы, получившие название «альтернативные каркасные белки» (АКБ) или «скаффолды» и отвечающие всем требованиям для оптимальной доставки радионуклида к опухолевым клеткам. Обычно АКБ имеют меньшие размеры по сравнению с антителом, но большие, чем пептиды, и характеризуются высокой аффинностью и оптимальными биохимическими, биофизическими, биологическими и экономическими характеристиками. Преимуществами таких белков являются их стабильная структура, хорошее проникновение в ткани, возможность дополнительной функционализации и ýкспрессия в бактериальной системе, обеспечивающая низкую стоимость производства.Результаты проведенных к настоящему моменту доклинических и клинических исследований для диагностики злокачественных образований с использованием таких представителей АКБ, как аффибоди, аднектин, дарпины и пр., продемонстрировали высокую специфичность, аффинность, хорошую переносимость и низкую иммуногенность используемых препаратов.

РАДИОНУКЛИДНЫЕ МЕТОДЫ ИССЛЕДОВАНИЯ В ДИАГНОСТИКЕ РАКА ГОРТАНИ И ГОРТАНОГЛОТКИ

Introduction. The choice of adequate treatment for cancer patients and their survival rates signifcantly depend on the precise detection of the primary tumor and the assessment of the extent of cancer involvement. Despite advances in the treatment of laryngeal/hypopharyngeal cancer, many aspects of this problem are still unresolved. The purpose of the study. Diagnostic capabilities of nuclear medicine imaging in the detection and assessment of the spread of laryngeal/hypopharyngeal cancer were studied. Material and methods. The study included 40 patients with histologically verifed laryngeal/ hypopharyngeal cancer, 10 patients with tumor recurrence after completion of therapy and 20 patients with benign laryngeal lesions. Single photon emission computed tomography (SPECT) was performed 20 minutes after the injection of 99mTc-methoxy-isobutyl-isonitrile (MIBI). Sentinel lymph nodes (SLNs) were detected in 26 patients after submucosal injections of 99mTc-Tehneft or 99mTc-Alotech around the tumor. In 18 hours after the injection of 99mTc-Tehneft and 99mTc-Alotech, SPECT was performed. In 24 hours after the injection of 99mTc-Tehneft and 99mTc-Alotech, intraoperative SLN detection was performed using Gamma Finder II. Results. SPECT with 99mTc-MIBI revealed laryngeal and hypopharyngeal tumors in 38 of the 40 patients. The 99mTc-MIBI uptake in metastatic lymph nodes was visualized in 2 (17 %) of the 12 patients. 28 SLNs were detected by SPECT and 31 SLNs were identifed using the intraoperative gamma probe. The percentage of lymphotropic radiopharmaceuticals in the SLN was 5–10 % of the radioactivity in the injection site by SPECT and 12–33 % by intraoperative gamma probe detection. Conclusion. SPECT with 99mTc-MIBI is an effective tool for the diagnosis of laryngeal/hypopharyngeal cancer. The sensitivity, specifcity and accuracy of this technique were 95, 80 and 92 %, respectively. The use of 99mTc-Tehnefte and 99mTc-Alotech for the detection of SLN in laryngeal/hypopharyngeal cancer patients was characterized by high effcacy, while intraoperative detection was more sensitive, being 80 and 100 %, respectively.Введение. Выбор адекватной тактики лечения и показатели выживаемости при злокачественных новообразованиях в значительной мере зависят от точности диагностики первичной опухоли. Несмотря на значительные успехи, достигнутые в лечении рака гортани и гортаноглотки, многие аспекты этой проблемы до сих пор остаются нерешенными. Цель исследования – оценка диагностических возможностей радионуклидных методов в визуализации оценки распространенности злокачественных опухолей гортани и гортаноглотки. Материал и методы. В исследование было включено 40 пациентов с раком гортани или гортаноглотки, 10 больных с рецидивом опухолевого процесса, а также 20 человек с доброкачественной патологией гортани. В качестве радиофармпрепаратов использовались 99mTcметоксиизобутил изонитрил (МИБИ), 99mTc-Технефит и 99mTc-«Aлотех». Через 20 мин после введения 99mTc-МИБИ проводилась однофотонная компьютерная томография (ОФЭКТ). Детекцию сторожевых лимфатических узлов (СЛУ) проводили у 26 больных. Через 18 ч после введения 99mTc-Технефита или 99mTc-«Aлотех» выполнялась ОФЭКТ, через 24 ч осуществлялось интраоперационное выявление сторожевых лимфатических узлов при помощи гамма-зонда Gamma Finder II (США). Результаты. При выполнении ОФЭКТ с 99mTc-МИБИ удалось выявить патологическое образование в области гортани или гортаноглотки у 38 пациентов из 40. Накопление препарата в проекции лимфоузлов, пораженных метастазами, удалось визуализировать у 2 (17 %) человек из 12 обследованных. При визуализации СЛУ по данным ОФЭКТ у 26 пациентов выявлены 28 лимфоузлов, при интраоперационной детекции выявлен 31 СЛУ. Интенсивность включения лимфотропных препаратов в СЛУ при ОФЭКТ составляла 5–10 % от места введения, при интраоперационной радиометрии – 12–33 %. Заключение. ОФЭКТ с 99mTc-МИБИ является высокоэффективным методом диагностики злокачественных опухолей гортани и гортаноглотки, чувствительность, специфичность и точность данного метода составляют 95, 80 и 92 % соответственно. Использование 99mTc-Технефита и 99mTc-«Aлотех» для диагностики СЛУ при раке гортани и гортаноглотки характеризуется высокой эффективностью, при этом большей чувствительностью обладала интраоперационная детекция, которая составила 80 и 100 % соответственно.

RADIOPHARMACEUTICALS BASED ON THE GLUCOSE DERIVATIVES FOR TUMOR DIAGNOSIS

The purpose of the study was to review available literature on the efficacy of radiopharmaceuticals based on glucose derivatives labeled with radioactive isotopes for detection of various cancers. Material and methods. A systematic literature review was performed using the Scopus, Web of Science, MedLine, Cochrane Library, EMBASE, and Global Health databases from 2000 to 2016. Out of 900 papers in the field of nuclear medicine, 58 were included into the review. Results. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) has been approved to be a powerful imaging tool for the detection of various cancers as well as for the assessment of tumor extent and therapy response. There is a continuous search for new more specific and effective radiopharmaceuticals for visualization of tumor tissue. Many studies are devoted to the development of radiopharmaceuticals based on technetium-99m labeled glucose derivatives for tumor visualization. Russian researches have made a significant progress in the development of imaging agents for single-photon emission computed tomography. Conclusion. Despite the widespread use of positron emission tomography technologies, which have proved to be effective, the specialists still have a great interest in radiopharmaceuticals based on technetium-99m. The literature review suggests that the emergence of a diagnostic radiopharmaceutical based on technetium-99m labeled glucose derivative will help to improve the availability of nuclear medicine methods and their effectiveness

Alternative scaffolds in radionuclide diagnosis of malignancies

This review discusses a relatively new class of targeted molecules that is being actively studied for radionuclide diagnosis and treatment of malignancies. The full-size antibodies used so far have non-optimal pharmacological properties, slow distribution in the body, poor penetration into the tissue and kidney excretion, and high immunogenicity, which significantly complicates their use in clinical practice. Over the past decade, a new class of targeted molecules, called “non-immunoglobulin scaffolds” have become popular; they have all the requirements for optimal delivery of a radionuclide to tumor cells. Scaffolds usually are smaller in size in comparison with antibodies, but they are larger than peptides, and are characterized by high affinity and optimal biochemical, biophysical, biological, and economic features. The advantages of such proteins are their stable structure, good penetration into tissues, the possibility of additional functionalization and expression in the bacterial system, which ensures low production costs.The results of preclinical and clinical studies for diagnosis of malignancies using such proteins as affibody, adnectin, DARPins, etc., have demonstrated their high specificity, affinity, good tolerance and low immunogenicity