surgoncoКреативная хирургия и онкологияCreative surgery and oncology2076-30932307-0501Башкирский государственный медицинский университет10.24060/2076-3093-2018-8-3-176-184surgonco-328Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL ARTICLESКомплекс индоцианина зеленого с аргинин-глицин-аспарагиновой кислотой как новый метод интраоперационной визуализации при резекции рака мочевого пузыряIndocyanine Green and Arginine-Glycine-Aspartic Acid Complex Used in Intraoperative Visualization during Resection of Bladder TumourПэнгЛиPengLi

аспирант урологического отделения больницы № 4, Китай, 150081, Хэйлунцзян, Харбин, Наньган, Баоцзянь-роуд, 157.

Post-graduate student of the Department of Urology of the Fourth Affiliated Hospital, 157 Baojian Rd, Nangang Qu, Haerbin Shi, Heilongjiang Sheng, 150081, China.

15636152446@163.comКабировИ. Р.KabirovI. R.

аспирант урологического отделения больницы № 4, ассистент кафедры урологии, тел.: +7 (917) 422-58-81, Россия, 450008, Уфа, ул. Ленина, 3.

Post-graduate student of the Department of Urology of the Fourth Affiliated Hospital; Assistant lecturer of the Department of Urology, 3 Lenin str., Ufa, 450008, Russian Federation.

ldarkabirov@gmail.comКасинскаяА. Р.KasinskayaA. R.

аспирант кафедры урологии, тел.: +7 (905) 353-49-50, Россия, 450008, Уфа, ул. Ленина, 3.

Post-graduate student of the Department of Urology, tel.: +7 (905) 353-49-50,  3 Lenin str., Ufa, 450008, Russian Federation.

adelina-fly@rambler.ruВанДжичиWangJiaqi

врач урологического отделения больницы № 4, Китай, 150081, Хэйлунцзян, Харбин, Наньган, Баоцзянь-роуд, 157.

Physician of the Department of Urology of the Fourth Affiliated Hospital, 157 Baojian Rd, Nangang Qu, Haerbin Shi, Heilongjiang Sheng, 150081, China.

346290658@qq.comСюВанхайXuWanhai

профессор, зав. кафедры урологии, вице-президент больницы № 4,  Китай, 150081, Хэйлунцзян, Харбин, Наньган, Баоцзянь-роуд, 157.

Professor, Head of the Department of Urology, Vice-president of the Fourth Affiliated Hospital, 157 Baojian Rd, Nangang Qu, Haerbin Shi, Heilongjiang Sheng, 150081, China.

xuwanhai@163.comЖукЕ. И.ZhukE. K.

студент 4 курса лечебного факультета, тел.: +7 (917) 359-48-30, Россия, 450008, Уфа, ул. Ленина, 3.

Fourth-year-student of the Faculty of General Medicine, tel.:+7 (917) 359-48-30, 3 Lenin str., Ufa, 450008, Russian Federation. 

Zhukketrin@yandex.ruНуралиеваР. А.NuralievaR. A.

студент 4 курса лечебного факультета, Россия, 450008, Уфа, ул. Ленина, 3.

Fourth-year-student of the Faculty of General Medicine, 3 Lenin str., Ufa, 450008, Russian Federation. 

Nayka606@mail.ruХарбинский медицинский университет.КитайHarbin Medical University.ChinaБашкирский государственный медицинский университет.РоссияBashkir State Medical University.Russian Federation20182501201983176184Copyright © Пэнг Л., Кабиров И.Р., Касинская А.Р., Ван Д., Сю В., Жук Е.И., Нуралиева Р.А., 20192019Пэнг Л., Кабиров И.Р., Касинская А.Р., Ван Д., Сю В., Жук Е.И., Нуралиева Р.А.Peng L., Kabirov I.R., Kasinskaya A.R., Wang J., Xu W., Zhuk E.K., Nuralieva R.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surgonco.ru/jour/article/view/328

Введение. Рак мочевого пузыря является одним из наиболее распространенных злокачественных новообразований, приносящих значительный экономический и социальный ущерб человеку. Для решения данной проблемы предложено использование высокочувствительного метода обнаружения рака мочевого пузыря, выявления остаточной опухоли и определения границ опухоли мочевого пузыря — интраоперационной флюоресцентной молекулярной визуализации. Ранее нами синтезирован таргетный агент — индоцианина зеленого-аргинин-глицин-аспарагиновая кислота, которая является интегрин avß3-целенаправленной в in vitro и in vivo моделях рака мочевого пузыря.Материалы и методы. Токсичность индоцианина зеленого-аргинина-глицин-аспарагиновой кислоты (АГАк-ИЦЗ) была измерена с помощью МТТ-теста. Самки BALB/nu и клеточные линии MB49 уротелиальной карциномы мыши использовали для установки опухолевых ксенотрансплантатов, инъекцией в заднюю локтевую область. Рост опухоли наблюдался ежедневно и проверялся магнитно-резонансной томографией, пока он не становился подходящим для экспериментов in vivo. Далее лабораторные животные были разделены на 2 группы: ИЦЗ и АГАк-ИЦЗ (150 мкл, 0,2 мг/мл для всех мышей). Затем проводилось хирургическое удаление опухоли. Удаленную ткань подвергали флюоресцентной микроскопии на основе ближневолнового инфракрасного спектра и гистологическому исследованию.Результаты. Операции, проведенные на подкожной и ортотопической мышиных моделях под контролем флюоресцентной визуализации с использованием АГАк-ИЦЗ, демонстрируют эффективность использования прицельной опухолевой пробы для достижения аккуратной и точной РМП резекции. Операции под контролем БИК-спектрометрии продемонстрировали, что предлагаемое вещество может эффективно помочь хирургам найти опухоль, определить край опухоли и постоянно проверять наличие остатков опухоли во время операции.Заключение. Таким образом, по результатам исследования продемонстрирована высокая эффективность АГАк-ИЦЗ как потенциального молекулярного флюоресцентного агента для опухолеспецифичной интраоперационной визуализации при резекции рака мочевого пузыря и большой потенциал для проведения дальнейших клинических исследований.

Introduction. Bladder cancer is one of the most common malignancies in humans, causing significant economic and social damage. In the connection, it is proposed to use a highly sensitive bladder cancer detection method, which also detects residual tumours. Additionally, the method can be used to determine the boundaries of the bladder tumour, namely through intraoperative fluorescence molecular imaging. The target agent was synthesised earlier with indocyanine green-arginine-glycine-aspartic acid, which is an integrin avß3-targeted in in vitro and in vivo bladder cancer models.Materials and methods. The toxicity of indocyanine green-arginine-glycine-aspartic acid (Agac-IG) was measured using the MTT-test. Urothelial carcinoma cell lines were introduced in Female BALB/nu and MB49 mice by means of tumour xenografts via injection in the back of the elbow area. Tumour growth was observed on a daily basis and tested by magnetic resonance imaging until it became suitable for in vivo experiments. Then, all the laboratory animals were divided into 2 groups: ig and AGAk-ig (150 μl, 0.2 mg/ml for all mice). Following this, the tumour was surgically removed. The removed tissue was subjected to a fluorescent microscopy on the basis of infrared-spectrum and histologic studies.Results. Operations carried out on subcutaneous and orthotopic mouse models under the control of fluorescent imaging using AGAk-IG demonstrate the effectiveness of using a targeted tumour sample to achieve consistent and accurate RMP-resection. Operations under the control of BIC-spectrometry have demonstrated that the proposed substance can effectively help surgeons to locate tumours, determine their edges and constantly check the presence of tumour residues during surgery.Conclusion. The findings demonstrated the high efficiency of AGAk-IG as a potential molecular fluorescent agent for tumour-specific intraoperative imaging in bladder cancer resection, as well as offering great potential for further clinical studies.

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The authors declare that there are no conflicts of interest present.