Medical Radiology and radiation safety Medical Radiology and radiation safety Медицинская радиология и радиационная безопасность 1024-6177 2618-9615 28615 10.12737/article_5cf237bf846b67.57514871 Протонная терапия Proton therapy Протонная терапия Prospects of Proton Therapy Combined Technologies in the Treatment of Cancer Перспективы применения комбинированных технологий в протонной терапии злокачественных новообразований Бушманов А. Ю. Bushmanov A. Yu.

доктор медицинских наук;

doctor of medical sciences;

 Шейно И. Н. Sheino I. N.

кандидат физико-математических наук;

candidate of physical and mathematical sciences;

 Липенгольц А. А. Lipengolts A. A.

кандидат физико-математических наук;

candidate of physical and mathematical sciences;

 Соловьев А. Н. Solovev A. N.

кандидат физико-математических наук;

candidate of physical and mathematical sciences;

 Корякин С. Н. Koryakin S. N.

кандидат биологических наук;

candidate of sciences in biology;

 Федеральный медицинский биофизический центр им. А.И. Бурназяна ФМБА России Москва Россия A.I. Burnasyan Federal Medical Biophysical Center of FMBA Moscow Russian Federation Федеральный медицинский биофизический центр им. А.И. Бурназяна ФМБА России Москва Россия A.I. Burnasyan Federal Medical Biophysical Center of FMBA Moscow Russian Federation Федеральный медицинский биофизический центр им. А.И. Бурназяна ФМБА России Москва Россия A.I. Burnasyan Federal Medical Biophysical Center of FMBA Moscow Russian Federation Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина Минздрава России Москва Россия N.N. Blokhin National Medical Research Center of Oncology Moscow Russian Federation Медицинский радиологический научный центр им. А.Ф. Цыба Обнинск Россия A.F. Tsyb Medical Radiological Research Center Obninsk Russian Federation Медицинский радиологический научный центр им. А.Ф. Цыба Обнинск Россия A.F. Tsyb Medical Radiological Research Center Obninsk Russian Federation 64 3 11 18 https://zh-szf.ru/en/nauka/article/28615/view

Цель: Исследование возможностей увеличения эффективности протонной терапии за счет использования комбинированных (бинарных) технологий на снове совместного действия протонного излучения и специальных препаратов. Материал и методы: Аналитический обзор публикаций по исследованиям совместного действия протонного излучения и химических соединений, повышающих чувствительность опухолевой ткани к облучению. Результаты: За последние годы исследования повышения эффективности протонной терапии за счет использования препаратов, содержащих элементы с аномально высокими по отношению к биоткани сечениями взаимодействия протонов, проводились в двух направлениях: 1) использование ядерных реакций с образованием частиц с высокой ЛПЭ на протонах низких энергий для локализации дополнительной дозы в пике Брэгга; 2) использование процессов взаимодействия протонов и вторичных электронов его трека с наночастицами металлов с Z>52, что обеспечивает перераспределение выделенной в тканях энергии и ее локализации в опухоли. Однако небольшое количество проведенных исследований ядерной реакции 11В(p,3a) в протонной терапии и противоречивость их результатов пока не позволяют сделать окончательный вывод о перспективности использования препаратов на основе бора-11 для повышения терапевтической эффективности протонной терапии. Однако привлекательность такого подхода определяется наличием клинически испытанных бор-содержащих препаратов и их успешным применением в борной нейтронозахватной терапии. Проведенный анализ применения наночастиц металлов в исследованиях возможностей их использования в радиационной терапии показал, что, несмотря на многообещающие результаты доклинических исследований, представленные в многочисленных публикациях, до этапа клинических испытаний фазы I/II дошли только три препарата на основе наночастиц металлов. Причиной этого является факт, что механизм радиосенсибилизации, лежащий в основе предлагаемой технологии, еще до конца не изучен и не формализован. Не определены количественные соотношения между свойствами наночастиц (материал, форма, покрытие и др.), способами облучения и биологическим эффектом, в том числе и в плане терапевтической эффективности. Заключение: Необходимо проведение как фундаментальных, так и прикладных исследований для описания процессов, лежащих в основе комбинированных технологий радиационной терапии. Это позволит решить как проблему планирования лучевой терапии, принятой в существующей практике, так и проблему прогнозирования результатов применения комбинированной протонной терапии в лечении злокачественных опухолей.

Purpose: Evaluating the possibilities to increase proton radiotherapy therapeutic efficacy by means of combined (binary) technologies: simultaneous application of proton radiation and special drugs. Material and methods: Published studies assessing antitumor efficacy of proton radiation together with simultaneous tumor radiosensitizing chemical compounds administration in treating cancer are being reviewed and analyzed. Results: Two approaches to increase therapeutic efficacy of proton radiotherapy using drugs, which have abnormally large value of proton interaction cross section comparing to soft tissues, can be outlined recently. They are: 1) utilization of proton induced nuclear reactions producing high LET secondary radiation to increase absorbed dose in tumor; 2) utilization of protons and proton track’s secondary electrons interaction with high-Z nanoparticles (Z>52), that leads to redistribution of released proton energy in soft tissues and its localization in tumor volume. Limited number of the studies devoted to application of 11B(p,3a) nuclear reaction in proton therapy and contradictoriness of the obtained result do not allow to judge so far about the future prospects of the boron containing drugs utilization in proton therapy to increase its antitumor efficacy. However, this approach looks very attractive because of the already existing boron drugs successfully being applied in boron neutron capture therapy. Analysis of the metal nanoparticle application in radiotherapy showed that despite of the promising results showing impressive tumor suppression increase represented in many scientific papers only three pharmaceuticals based on nanoparticles reached Phase I/II Clinical Trials. Radiosensitizing mechanism of metal nanoparticles in radiotherapy is still unrevealed, unstudied and not formalized thus interfering nanoparticle based pharmaceuticals to be approved for Clinical Trials. Quantitative relationship between nanoparticles’ properties (i.e. chemical composition, shape, surface coating etc.), irradiation parameters and final biological effect (therapeutic efficacy) is still undetermined. Conclusion: Fundamental and applied studies should be carried out to determine and describe the processes underlying in the basis of combined methods of proton radiotherapy. That would allow to perform both proper treatment planning, similar to conventional radiotherapy, as well as the prognosis of the therapy final outcomes in curing malignant tumors.

 протонная терапия радиосенсибилизация бор-11 наночастицы proton therapy radiosensitization radioenhancement boron-11 nanomedicine nanoparticles

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