Objectives . Due to the increasing number of oncological diseases, active research into developing new radiopharmaceuticals is underway. Thermosensitive copolymers have valuable physicochemical properties that can be harnessed to develop therapeutic radiopharmaceuticals for treating solid tumors. The aim of this study was to develop a method for producing thermosensitive copolymers that can find use as radionuclide carriers to create therapeutic radiopharmaceuticals for treating solid tumors. Methods . Using radical copolymerization in polar solvents, we synthesized water-soluble copolymers based on N-isopropyl acrylamide and 2-aminoethyl methacrylate hydrochloride. The resulting copolymers were characterized in terms of molecular composition and hydrodynamic properties using gel permeation chromatography, IR spectroscopy, potentiometry, and viscometry. Changes in optical density during temperature scanning helped determine the phase transition temperature (PTT) of aqueous copolymer solutions. Results . We developed a method for preparing copolymers of N-isopropylacrylamide with 2-aminoethyl methacrylate using radical copolymerization in water and isopropanol with a content of 2-aminoethyl methacrylate hydrochloride in a copolymer up to 23 mol %. We studied how the second comonomer affected the PTT of the aqueous copolymer solutions. An increase in the content of 2-aminoethyl methacrylate in the copolymer caused the PTT to increase. We found that the change in the PTT depending on the content of 2-aminoethyl methacrylate units in the copolymer had a straightforward relationship with its content up to 17 mol %. The use of physiological saline as a solvent led to a temperature decrease of the phase transition by two degrees. Conclusions . The method of producing thermosensitive copolymers by radical copolymerization in isopropanol does not allow creating a radionuclide carrier. Solutions of the obtained lowmolecular weight oligomers form coacervate solutions, which will inevitably cause the radionuclide to spread throughout the body. The copolymers obtained by radical copolymerization in water with the content of the second comonomer 2-aminoethyl methacrylate from 10–17 mol % can be used as a radionuclides carrier provided that a physiological solution of sodium chloride is used as a solvent.

Фармакокинетические свойства и противоопухолевая эффективность нового радиофармпрепарата на основе 153 Sm в термочувствительном носителе на опухолевой модели гепатохолангиомы РС-1

This work is devoted to studying the in vivo antitumor efficacy of the new injection radiopharmaceutical based on thermoresponsive polymer and β−-emitting radionuclide samarium-153 (153Sm-KARP-CheM). The study of in vivo antitumor efficacy was performed using mice F1 and C57Bl/6 with transplanted subcutaneously sarcoma S37 and melanoma B16, respectively. The animals received single intratumoral bolus injections of 37 MBq (1 mCi), or 18.5 MBq (0.5 mCi) of 153Sm-KARP-CheM, or saline in a volume 0.1 ml. The efficacy of antitumor treatment was evaluated using tumor growth inhibition index (TGI, %) and increase of average life span (ILS, %). The most meaningful therapeutic efficacy after intratumoral injection of 153Sm-KARPCheM was observed in melanoma-bearing mice C57Bl/6. The highest values of TGI for melanoma B16 were 79.5% and 79.6% after treatment with 18.5 MBq or 37 MBq, respectively. An increase of average life span by 17.1% was found in group of melanoma-bearing mice treated with 37 MBq of 153Sm-KARP-CheM only. Tumor growth inhibition of sarcoma S37 was slightly lower as compared with melanoma B16: 62.5% and 59.0% in 37 MBq and 18.5 MBq groups, respectively. 153Sm-KARP-CheM didn’t increase average life span of treated animals. In conclusion, 153Sm-KARP-CheM seems to be effective radiopharmaceutical for local tumor radiotherapy.

Новый радиофармпрепарат на основе термочувствительного полимера и 153 Sm для локальной радионуклидной терапии солидных опухолейПетриев В.М. 1,2, Тищенко В.К. 1 , Сморызанова О.А. 1 , Михайловская А.А. 1 , Больбит Н.М. 3 , Дуфлот В.Р. 3 , Гайворонский А.В. 3 , Морозова Н.Б. 4 , Якубовская Р.И. 4  1 МРНЦ им.А.Ф.Цыба -филиал ФГБУ «НМИЦ радиологии» Минздрава России, Обнинск; 2 Национальный исследовательский ядерный университет «МИФИ», Москва; 3 АО «НИФХИ им.Л.Я.Карпова», Обнинск; 4 МНИОИ им.П.А.Герцена -филиал ФГБУ «НМИЦ радиологии» Минздрава России, Москва Данная работа посвящена изучению фармакокинетических свойств нового радиофармпрепарата на основе термочувствительного полимера и153 Sm ( 153 Sm-КАРП-ХеМ) для локальной радиотерапии солидных опухолей.Изучение биораспределения проводилось на мышах F1 и C57Bl/6 с имплантированными подкожно саркомой S37 и меланомой В16 соответственно при внутриопухолевом введении препарата (0,18-0,37 МБк, 0,1 мл).Результаты показали, что наибольшее количество активности отмечается в опухолевой ткани (т.е.в месте введения препарата).Через 7 дней после инъекции уровень активности в ткани саркомы S37 составил 57,2% от введённой дозы, а в ткани меланомы В16 -42,2% от введённой дозы.При этом удержание меченого препарата опухолевой тканью саркомы S37 выше, чем тканью меланомы В16, особенно в поздние сроки исследования.Пиковое значение активности в печени составило 1,14%/г.Транзиторное увеличение концентрации меченого препарата наблюдалось в желудке (до 4,22%/г через 5 мин), лёгких (до 1,15%/г через 1 ч) и коже (до 1,34%/г через 1 ч), однако затем она быстро снижалась.Повышенный уровень активности отмечался в почках, поскольку большая часть её выводилась через мочевыделительную систему.Концентрация активности в щитовидной железе, селезёнке, сердце, головном мозге, тонком кишечнике, мышечной ткани и бедренной кости была ниже 1%/г в течение всего срока исследования.Статистически значимых различий между уровнями активности во внутренних органах и тканях у мышей с саркомой S37 и меланомой В16 практически не выявлено.Таким образом, полученные результаты предполагают возможность использования данного радиофармпрепарата для локальной терапии опухолей.

The terpolymerization of acrylonitrile, methyl acrylate, and itaconic acid mediated by a reversible addition-fragmentation chain transfer agent, dibenzyl trithiocarbonate, and initiated by AIBN at 80°C, potassium persulfate at 45–55°C, and radiolysis at 20°C is studied. In all the cases, polymerization proceeds via the pseudoliving mechanism, which is preserved up to ultimately high monomer conversions (80–90%). According to FTIR ATR and NMR spectroscopy, all the synthesized terpolymers are characterized by close monomer compositions and their degree of branching is too low to be detected spectroscopically. However, the thermal behaviors of terpolymers obtained by polymerizations at various temperatures are different, namely, the lower the temperature of terpolymer synthesis, the slower the thermooxidative stabilization processes occurring in it.

Изучено влияние условий синтеза полиакрилонитрила (природы растворителя, гомогенности реакционной среды и типа инициирования) на условия формирования полисопряженной системы при пиролизе полиакрилонитрила. Впервые осуществлен контролируемый синтез полиакрилонитрила радиационной полимеризацией в присутствии агента обратимой передачи цепи дибензилтритиокарбоната при 25 и 80°С. Показано, что тип инициирования в полимеризации с обратимой передачей цепи (вещественное или радиолиз) также оказывает существенное влияние на структуру образовавшейся полисопряженной системы.

The effect of the conditions of polyacrylonitrile synthesis (nature of the solvent, homogeneity of the reaction medium, and type of initiation) on the conditions of formation of the polyconjugation system during the pyrolysis of polyacrylonitrile is studied. The controlled synthesis of polyacrylonitrile via radiation polymerization mediated by dibenzyl trithiocarbonate as a reversible addition-fragmentation chain-transfer agent at 25 and 80°C is performed for the first time. It is shown that the type of initiation in reversible addition-fragmentation chain-transfer polymerization (material initiation or radiolysis) strongly affects the structure of the formed polyconjugation system.

The analysis of theoretical published data and our experimental data makes it possible to assume that the main difference between polyacrylonitriles prepared via emulsion and solution polymerization appears at the stage of synthesis. This difference is likely related to the freezing of the segmental mobility of strongly sorbed two-dimensional chains that grow in a reaction gap of the latex polymer-monomer particles that is narrow in comparison to the undisturbed spectrum of relaxation times of the three-dimensional entanglement network in the volume of polymerization solution. This factor is responsible for an increased concentration of long-chain branches in polyacrylonitrile formed in solution and, correspondingly, marked retardation of the viscous flow of concentrated polyacrylonitrile solutions.

A new cation exchange sorbent based on polyethylene powder modified by polyacrylic acid was prepared for technetium-99m generator column. The dependence of the kinetics of polyethylene modification on the structure of grafting solution was studied. The adsorption of manganese ions by the obtained sorbent has been studied. The new sorbent was tested in technetium-99m generator column with the maximum output activity. It is expedient to use the sorbent in a technetium-99m generator column in order to improve the quality of effluent, increase the stability of the yield of pertechnetate ions, and maintain the eluate medium in a condition close to neutral.

A combination of statistic and kinetic methods of analysis is used to collect quantitative data on the kinetics of elementary reactions of growth and termination of kinetic chains in each phase of a heterophase system as well as on interfacial mass exchange at the quasistationary stage of radiation-induced emulsion polymerization of acrylonitrile. It is found that, in the system, a steady-state concentration of polymer-monomer particles is attained, and these particles are able to increase their dimensions with an increase in monomer conversion. Activation of particles and chain termination on particles are due to the entrapment of macroradicals from water. As a result of a gradual increase in the dimensions of polymer-monomer particles and a decrease in the monomer concentration in the aqueous phase, the adsorption layer of acrylonitrile becomes so thin that, at the final stage, monomolecular layers lose integrity and the conditions of quasi-stationarity are violated.

In the article influence of the molecular weight of polyacrylonitrile on electrospinning process and also on the diameter and mechanical properties of the obtained fibers and fiber materials are considered. Polymers with molecular weight from 280 000 to 700 000 were investigated. Fibers with a diameter from 200 to 1100 nm were obtained.

Radiation-induced graft polymerization of acrylic acid onto powdered polyethylene samples of various granulometric compositions was studied. The resulting graft polymer can be used as a cation-exchange sorbent. The ion adsorption properties of the synthesized cation exchanger were characterized.

It was argued that, in the emulsion polymerization of poorly water-soluble monomers like styrene carried out in the presence of oil-soluble initiators, the principal initiation mechanism is the two-event paired reinitiation reaction. In terms of this mechanism, in a latex particle containing a macroradical, one radical of the radical pair arising from decomposition of the oil-soluble initiator undergoes recombination with the macroradical, while the other radical product initiates growth of a new chain via addition to a monomer molecule. The method for calculating the radical capture rate constant k(c) and the capture efficiency coefficient mu for radicals entrapped by monomer-swollen polymer particles from an aqueous phase was developed. It was found that for styrene kc approximate to (2 X 10(5))-(4 x 10(6)) 1/(mol s) and 0 < mu < 1, depending on the initiation rate of and the initiator type and concentration.

Gelation with the participation of a chromium salt in aqueous solutions of hydrolyzed polyacrylamide, sodium polymethacrylate, and their physical mixtures and copolymers produces a specific absorption band in the UV absorption spectra. The intensity of this band is proportional to the concentration of ion-coordination intermolecular crosslink complexes. The gelation points in solutions of the studied polymers are determined by the spectral method. They are compared to the overlap and entanglement concentrations determined from rheological data. By analyzing the latter data on the conceptual basis of the scaling theory of polyelectrolyte solutions, it became possible to classify the studied polymers into two groups according to the degree of the manifestation of ionization effects. The mechanism of the aging of polyelectrolyte solutions due to spontaneous formation of the physical junction network is substantiated.

The locally initiated emulsion photopolymerization of styrene in the presence of an oil-soluble photoinitiator was studied using a combination of kinetic and statistical analysis techniques. Based on the kinetic scheme of the process occurring in initiation and propagation reaction zones that greatly differ from one another in volume, the relative contributions of the following three reactions to the overall termination rate of macro-radicals were calculated: chain transfer and photoinduced chain transfer to the monomer and termination by small radicals generated in the aqueous phase from a molecularly dissolved photoinitiator. Using mathematical treatment of the molecular mass distribution of polymers, the statistical weights of these reactions were determined, which satisfactorily agree with those calculated in terms of the kinetic model. It was shown that ratios between the partial contributions vary with conversion and are strongly dependent on the light flux intensity.

The rates of radiation polymerization of styrene and MMA measured calorimetrically at the autoacceleration step inside of preliminary prepared methacrylate- and styrene-based polymer networks were compared with those calculated on the basis of the current theory of gel effect. In the case of styrene polymerization, the compared polymerization rates differ by two orders of magnitude for both matrices, methacrylate and styrene networks having strongly different crosslink densities, kinetic rigidities, and radiation sensitivities. In the case of MMA, a good fit is observed only for relatively loosely crosslinked methacrylate networks and, correspondingly, their high swelling ability. These effects are explained by the specifics of radiation-induced polymerization of vinyl monomers in densely crosslinked networks, which occurs under conditions of microphase separation and retardation of translational self-diffusion of propagating chains that are chemically bonded to the primary network.