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ТЕРАНОСТИКА - СОВРЕМЕННАЯ МОДЕЛЬ ЯДЕРНОЙ МЕДИЦИНЫ
Король П.А.
доктор медицинских наук, заведующий отделением радионуклидной диагностики Киевской городской клинической больницы № 12, Киев, Украина
Ткаченко М.Н.
доктор медицинских наук, профессор, заведующий кафедрой радиологии и радиационной медицины Национального медицинского университета имени А.А. Богомольца, Киев, Украина
THERANOSTICS - MODERN MODEL OF NUCLEAR MEDICINE
Korol P.
doctor of medical science, head of department of nuclear medicine of Kiev Clinical City
Hospital # 12, Kiev, Ukraine Tkachenko M.
doctor of medical science, professor, head of the department of radiology of Bohomolets National Medical
University, Kiev, Ukraine
Аннотация
С целью усовершенствования и развития концепции тераностики перспективно использовать сильные стороны ядерной медицины, путем разработки платформ для выявления новых биологических субстратов, прогнозирования возможных негативных последствий и предоставления практических средств, направленных на определение объективных и количественных критериев для мониторинга оценки качества терапевтических процедур. Препараты большинства химических или даже неорганических композиций, специфически предназначенных для тех или иных клеточных или биохимических мишеней, могут быть модифицированы в комплекс изображений путем соответствующей конъюгации с изображениями, полученными за счет современных синтезированных радионуклидов.
Тераностика, как современная модель ядерной медицины может активно использоваться в практической и научной работе отделений радионуклидной диагностики и ядерной медицины, онкологии, урологии и других отделений. Предложенная концепция также полезной для наблюдения за изменениями злокачественной опухоли в динамике, при контроле качества лечения онкологических больных.
Abstract
In order to improve and develop the concept of theranostics, it is promising to use the strengths of nuclear medicine, by developing platforms for identifying new biological substrates, predicting possible negative consequences and providing practical tools aimed at determining objective and quantitative criteria for monitoring the evaluation of the quality of therapeutic procedures. Preparations of most chemical or even inorganic compositions specifically designed for particular cellular or biochemical targets can be modified into a complex of images by appropriate conjugation with images obtained from modern synthesized radionuclide.
Theranostics as a modern model of nuclear medicine can be actively used in the practical and scientific work of the radionuclide diagnostics and nuclear medicine, oncology, urology and other departments. The proposed concept is also useful for monitoring changes in a malignant tumor in dynamics, while monitoring the quality of treatment for cancer patients.
Ключевые слова: тераностика, ядерная медицина, радиофармпрепарат, позитронно-эмиссионная томография.
Keywords: theranostics, nuclear medicine, radiopharmaceutical, positron emission tomography.
Theranostics - a new approach to the creation of pharmaceutical compositions, which is the ability to comprehensively solve therapeutic and diagnostic problems by finding drugs that are both an early diagnostic tool, as well and a therapeutic agent.
The concept of theranostics: "We see what we treat, we see that we treat, we treat what we see." A typical example of this approach is the ultrasound detection of cancerous cells that circulate in the blood with their simultaneous destruction, which can slow down the development of metastases and cause more than 90% of deaths from cancer. It is these matters that deal with nuclear medicine. Nuclear medicine is an integral part of the modern medical medical diagnostic
process. For diagnostic purposes in nuclear medicine, radioactive nuclides labeled with "carriers" are labeled with biomolecules, followed by an assessment of their distribution in the patient's body using single-photon emission computed tomography (SPECT) or positron emission tomography (PET), which ensures the collection of Capacitive imaging and quantitative parameters that can be used to diagnose a wide range of diseases and/or evaluate reactive changes in organs and tissues during treatment and diagnostic measures [10, 26].
The use of nuclear medicine for therapeutic purposes, previously known as the radio-metabolic therapy, consists in replacing radionuclides that have been
used for diagnostic purposes with alternative radionu-clides that provide "therapeutic" types of radiation, such as beta or alpha particles [18]. Active development and application of modern gamma emitters also allows for high-quality scintigraphic visualization, which is a prognostic factor in the context of monitoring the distribution of radioactive substances in the patient's body [21]. For the first time in the history of nuclear medicine, the clinical use of radioactive isotopes for therapeutic purposes was carried out in the early 40s of the last century, when 32F was used to treat polycythemia and some forms of leukemia [11, 14].
Subsequently, for the therapeutic purpose in clinical practice, 13II was used for radioabsorption of residual tissue of the thyroid gland (after thyroidectomy) of patients with differentiated thyroid cancer [11, 12]. Since then, the method of radionuclide use for a therapeutic purpose has been a long and successful way; many classes of radiopharmaceuticals (RF) have been synthesized - from receptor [14] to monoclonal antibodies [8, 9].
According to empirical data of scientific researchers, the use of RF for therapeutic purposes has a very low level of carcinogenic risk and malignant transformation, sufficient, for example, to initiate a malignant tumor, which is why it is often used to treat benign diseases [5, 9]. More recently, at the international level, in particular in the United States, more than one hundred research trials have been carried out on the use of a number of radiopharmaceuticals for medical purposes [5]. Nuclear medicine practitioners have practiced this form of combined diagnostic and therapeutic measures for several decades through the use of known thyroid selective properties of 131I or molecular analogs of norepinephrine, as well as the engineering of biological compounds such as peptides that are specific for soma-tostatin receptors [15].
The calculation of radiation absorbed by body tissues is a guarantee of the success of radiological treatment [19, 20]. The aim is to evaluate the radioactivity of RF that are administered to the patient to provide the maximum therapeutic effect, but at the same time limit the excessive exposure of healthy tissues (especially the bone marrow and the kidneys). As mentioned earlier, RF of therapeutic radioactivity labeled with a radiation label (beta or alpha particle, as well as modern gamma emitters) are successfully used in clinical practice. Radiopharmaceuticals labeled with different radioactive compounds, in particular, gamma emitters, are used in clinical practice for diagnostic purposes while alpha and beta emitters are therapeutic for routine use in nuclear medicine [27]. As beta-emitting radioactive isotopes, for example, ionizing reactive oxygen species, which cause single-chain damage to genetic structures, are used. Alpha emitters, detached from the nucleus of specific radioactive isotopes, can lead to catastrophic cell damage on their path. They radiate at a short linear distance (several cell diameters) from the decomposing nucleus and form a very large amount of energy in the way they pass [2]. Some authors noted the effectiveness of molecular-targeting therapy with alpha emitters in various preclinical and clinical settings. For example, Wild et al. directly compared the efficacy and
toxicity of the bombesin peptide labeled by the emitter of a-particles (213Bi) or the emitter of p-particles (177Lu) in the preclinical model (malignant tumor of the prostate gland initiated in mice). The researchers observed that treatment with alpha emitters has a 100% therapeutic effect rate (70% complete and 30% partial) compared with 30% effective (20% complete and 10% partial) for beta-emitting therapy, indicating the power of the use of molecular-targeted therapy of high energy sources [3]. Several research protocols considered radi-onuclide therapy in combination with the use of far-range radiotherapy. It was expected that the effect of irradiation with a high dose external beam could change in irradiated areas of absorption of radiopharmaceuti-cals, tropical to bone tissue [16].
The current definition of the term "theranostics" consists in the combination of the introduction of a gamma-labeled labeled biomolecule for the purpose of diagnostic scintigraphic visualization and the subsequent administration of the same molecule labeled with radionuclide beta or alpha-emitter for therapeutic purposes [28]. From the historical point of view, the concept underlying the strategy of theranostics is well known in nuclear medicine and laid the foundations for many nuclear visualization procedures that are currently used in clinical practice [4]. For example, the use of peptides in radio physics and nuclear medicine has been considered by scientists for more than 20 years. Despite the considerable efforts of researchers in these fields of science, only radioactive peptides based on so-matostatin have effective therapeutic applications in nuclear medicine [16]. For example, 111-Indiethylene-triaminepentaacetic acid - a particular antidote is commercially available compound for radionuclide studies [4]. Diagnostic visualization has been greatly improved by the introduction of PET radionuclides such as 68Ga, 64Cu and 18F. Two peptides are successfully used in target radionuclide therapy when linked to somatostatin and the labels 90Y and 177Lu [3, 13, 17]. For the purpose of radionuclide diagnostics, not only gamma-emitting radionuclides that are well known to nuclear medicine specialists, as well as positron nuclides, which help to effectively solve the problem of tumor staging and restoration using PET/CT machines, are used. At the present stage, the molecular imaging in the form of PET with 18-FDG (18-fluorodisocysglucose) is practiced, which has become a revolution in practical nuclear medicine, and has become urgent precisely in cancer practice. The role of PET with 18-FDG, which is now synonymous with molecular imaging, has become an integral part of the diagnostic visualization of cancer patients, in particular, for the purpose of the staging and restoration of malignant tumors, as well as monitoring the response to therapy for a large number of indications [6].
Modern methods of diagnostic visualization in nuclear medicine include, first of all, the use of PET and SPECT using positron and gamma-rays of radionu-clides to generate a signal [29]. It should be noted that qualitative planning of external and internal radiation therapy can be directed at the diagnostic support of PET and SPECT. Accordingly, diagnostic visualization and
radiotherapy are mutually integrated into the conceptual model of theranostics, which leads to a more personalized approach to nuclear medicine [24]. Most of the positron markers are made on cyclotrons, so it is desirable that the production site is located at a close distance from the departments of nuclear medicine, which enables the "satellite" scheme to quickly deliver the RF to laboratories that do not have a cyclotron. PET/CT and PET/MRI research are promising diagnostic visualization methods for optimizing radiation therapy planning, providing an individual approach to each patient, as well as monitoring the assessment of quality control of treatment by applying a prior therapeutic assessment, and measuring the treatment response after radionuclide therapy [22] . On the other hand, radionuclide generator systems that provide an alternative
pathway to radionuclides that are used in clinical practice are the most widely used in nuclear medicine departments. The 99Mo/99mTc system continues to be the main source of diagnostic radioactive drugs and, today, covers about 80% of all radionuclide medical treatments around the world. Along with the routine application of 99Mo/99mTc in nuclear medicine to its subsidiary nuclide, which emits low-energy photon radiation and is actively used in diagnostic scintigraphic imaging [1], the recent interest of researchers has focused on potentially new analog-based generating systems.
For molecular imaging using PET, they become widely used, for example, generators 68Ge/68Ga and 82Sr/82Rb, etc. (Fig. 1).
Anterior
Fig.1. A - PET/CT from 68Ga-PSMA-11 patient C. with prostate cancer T4N3M1 (08/2015). B - PET/CT with 68Ga-PSMA-11 course of treatment 177Lu-PSMA activity of 6.4 GBq (04/2016).
Consequently, in the context of generator positron radiated radionuclides, the theory of terrorism is also true and relevant. Thus, the concept of theranostics is aimed at the promising use of the strengths of nuclear medicine by developing platforms for the detection of new biological substrates, prediction of possible negative consequences, and the provision of practical tools aimed at identifying objective and quantitative criteria for monitoring the evaluation of the quality of therapeutic procedures. The preparations of most chemical or even inorganic compositions specifically intended for one or another cellular or biochemical target can be modified into a complex of images by appropriate conjugation with images obtained from modern synthesized radionuclides. This key concept also emphasizes the value of the latest generation of potentially transformed biomedical materials that are scaled at the na-nometric level [15]. Nanoparticles represent an optimal platform of theranostics, mainly due to their modular construction. On a purely experimental basis, the model of theranostics has the ability to turn the therapeutic tracer into a diagnostic agent through appropriate and complex manipulations and marking with appropriate
radionuclide. This was demonstrated successfully by some authors who synthesized a positron tracer of the prostate gland from a therapeutic agent [23].
In conclusion, let's give a clinical example that demonstrates the conceptual stages of theranostics [7, 25].
1. A patient with clinical diagnosis: prostate cancer (T3N2M1). Laboratory parameters of PSA (Prostate Specific Antigen) = 2.9223 ng/ml. According to the diagnostic PET/CT with tumorotropic 68Ga-PSMA-11 (prostate-specific membrane antigen) - multiple metastases in the bone of the skeleton (12/2014). The next stage, the patient assigned three courses of radionuclide therapy 225Ac-PSMA activity of 6,4 GBq. 07/2015 -PET/CT monitoring with 68Ga-PSMA-11. Laboratory parameters of PSA (prostate specific antigen) = 0,26 ng/ml. The patient is recommended for a repeat therapy course of 225Ac-PSMA with 6,1 Gbq activity. 09/2015 - monitoring PET/CT with 68Ga-PSMA-11: lack of focal points for the accumulation of radiopharmaceuticals in the bones of the skeleton. Laboratory parameters of PSA (prostate-specific antigen) <0,1 ng/ml (Fig. 2).
7/2015 PSA • 0 26 »>o mi.
Fig. 2. A - PET/CT of 68Ga-PSMA-11 patient with cancer of the prostate T3N2M1 (12/2014). B - PET / CT with 68Ga-PSMA-11 after three treatment courses of225Ac-PSMA with activity of 6,4 GBq (07/2015). C - PET/CT with 68Ga-PSMA-11 after 225Ac-PSMA re-treatment with 6,1 Gbq activity (09/2015).
Thus, theranostics is ultra unique model of nuclear medicine, through which you can effectively solve therapeutic and diagnostic tasks through the use of drugs that are both as a means of early diagnosis and therapeutic agent. This model can be actively used in practical work and scientific departments radionuclide diagnostics and nuclear medicine, oncology, urology, and more. This concept is also useful for tracking changes in the dynamics of the malignant process, the quality control of treatment of cancer patients.
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ТАКТИКА ИНТЕНСИВНОЙ ТЕРАПИИ ПОЛИОРГАННОЙ НЕДОСТАТОЧНОСТИ У ДЕТЕЙ С ИНФЕКЦИОННОЙ ПАТОЛОГИЕЙ
Никонова Е.М.
к.м.н., доцент кафедры анестезиологии, интенсивной терапии и экстренной медицинской помощи, ГУ «Луганский государственный медицинский университет имени Святителя Луки», Луганск, Украина
Шатохина Я.П.
ассистент кафедры анестезиологии, интенсивной терапии и экстренной медицинской помощи, ГУ «Луганский государственный медицинский университет имени Святителя Луки», Луганск, Украина
TACTICS OF INTENSIVE CARE MULTIPLE ORGAN FAILURE IN CHILDREN WITH INFECTIOUS
PATHOLOGY
Nikonova E.M.
Assistant ofprofessor, Ph. D, department of anesthesiology, intensive care and emergency medicine, SE
«Lugansk State Medical University named after St. Luke», Lugansk, Ukraine
Shatokhina Y.P.
Assistant, department of anesthesiology, intensive care and emergency medicine, SE «Lugansk State Medical University named after St. Luke», Lugansk, Ukraine
Аннотация
В статье приведен анализ клинико-анамнестических, лабораторных и инструментальных данных, лечебных мероприятий у больных с полиорганной недостаточностью, находившихся на лечении в отделении интенсивной терапии детских инфекций. Намечены пути оптимизации лечения синдрома полиорганной недостаточности у детей с инфекционной патологией.
