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[en] Beta emitters are widely used in treatment of various oncological diseases for a long time. Alpha emitters belong to new and perspective candidates for therapeutic use and some of them have been already introduced into clinical practise. Targeted alpha-particle therapy (TAT) is a rapidly evolving field of cancer treatment. Nevertheless, there are some severe issues that prevent TAT from being a leading modality in radionuclide therapy. The nuclear recoil effect that causes the daughter nuclei release from the original radiopharmaceuticals is a critical problem for alpha emitters. Moreover, targeting and proper dosimetry is still an issue. Therefore, we focused on the dosimetry on cellular and subcellular level with an aim to quantitatively and qualitatively compare the effect of alpha and beta emitters on living cells. For our study we used Ra-223, Sm-153 and Re-186 as a model radionuclides. All radionuclides were used in the range 0-8 kBq/mL. Studied cell lines were V79 (Chinese hamster lung fibroblasts), DU145 (human adenocarcinoma cell line) and U87 (human primary glioblastoma cell line) obtained from American Type Culture Collection (ATCC). All cells were cultivated in humidified atmosphere under standard culture conditions (37℃, 5 % CO2). Chines hamster cell line (V79) was cultivated in Dulbecco’s Modified Eagle’s Medium (Sigma-Aldrich, Germany) supplemented with 10% of Fetal Bovine Serum South America Origin (Biosera, France) and 1% of Penicillin-Streptomycin (Biosera, France)). Human adenocarcinoma cell line (DU145) and human glioblastoma cell line (U87) were cultivated in Eagle’s minimum essential medium (Sigma- Aldrich, Germany) supplemented with 10% of Fetal Bovine Serum of South America Origin (Biosera, France), 1 % of Penicillin-Streptomycin (Biosera, France)), 1 % of L-glutamine (Sigma-Aldrich, Germany), 1 % of Nonessential amino acids (Sigma-Aldrich, Germany) and 1 % of pyruvate (Sigma-Aldrich, Germany). All cell lines have been cultivated in the presence of Ra-223, Sm-153 or Re-186 for 24 hours after the monolayer of the cells was created. After the cultivation with Ra-223, Sm-153 or Re-186, the clonogenic survival test was performed and survival curves for all cell lines were constructed. All obtained survival curves correspond to the linearly quadratic model. Sensitivity of both human carcinoma cell lines (adenocarcinoma and glioblastoma cell line) to treatment by all used radionuclides is higher than the sensitivity of the Chinese hamster pulmonary fibroblast cell line. Sensitivity of tested carcinoma or tissue cell lines is higher to alpha treatment than to beta treatment using the same applicated activities of alpha or beta emitters. The achieved results enabled further progress in enhancing the alpha dosimetric studies. (author)

[en] The Ge-68/Ga-68 radionuclide generator has a big perspective to become one of the most important sources of radionuclides for PET. Recently, available generators inorganic ion exchangers, especially titanium and tin oxides, are used as a stationary phase and diluted hydrochloric acid as eluent. Even though they provide Ga-68 in convenient chemical form, some of them do not provide it in a sufficient radionuclidic purity in one separation step as the Ph. Eur. limit for the mother radionuclide is 0.001%. This work was focused on the development of Ge-68/Ga-68 generator system based on the nanocomposites of cerium(IV) and zirconium(IV) in the polyacrylonitrile matrix. These perspective stationary phases should provide eluate in excellent quality. Cerium(IV), zirconium(IV) and titanium(IV) oxides and hydroxides were studied as potential active ion-exchanger components. All materials were characterized by X-ray powder diffraction, transmission and scanning electron microscopy, FT-IR and Raman spectrometry. Sorption properties of these materials were examined by the measurement of equilibrium distribution coefficients, Dw, of Ge-68 and Ga-68 in the presence of diluted hydrochloric acid (concentrations: 1 mol/l; 0.1 mol/l; 0.01 mol/l and 0.001 mol/l). On the basis of the separation factor, α, the optimal concentration of hydrochloric acid was determined and two materials with the best separation factor, cerium(IV) oxide and zirconium(IV) hydroxide, were granulated into the polyacrylonitrile matrix. Prepared composites were used for the construction of two model generators with bed volume of 0.57 ml and 1.6 MBq of Ge-68 and 1 MBq of Ge-68 for cerium(IV) oxide and for zirconium(IV) hydroxide, respectively. Elution curves, yields of elution and contamination percentages were determined for both prepared model generators.

[en] PSMA (Prostate-Specific Membrane Antigen) is a transmembrane protein which is overexpressed in most cases of prostate cancer. Expression level of this protein has a strong correlation to the stage of the disease, which makes PSMA a very attractive target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). One of the most promising radioligands for the treatment of mCRPC is a small-molecule-based PSMA-617 equipped with a DOTA chelator. PSMA-617 labelled with ¹⁷⁷Lu has been successfully applied in clinics. A recently introduced ¹⁶¹Tb has similar chemical and nuclear characteristics to ¹⁷⁷Lu, but also emits substantial amount of low-energy conversion and Auger electrons, which is believed to enhance therapeutic efficacy of the radiopharmaceutical. We optimized the reaction conditions for the labelling PSMA-617 with ¹⁶¹Tb and investigate the radiolytic stability of the labelled compound. Radiolabelling was achieved by adding [¹⁶¹Tb]TbCl³ (100-200 MBq) to the 1 mM water solution of PSMA-617 in acetate buffer (pH 4.5). Reaction mixture was stirred for 15-30 min at 95 °C. Radiochemical yield (98 %), as well as radiolytic stability, was studied by HPLC with radiometric detection. Reaction samples were measured every 24 hours. No stabilizing additives were used in this experiment. Promising ligand PSMA-617 was successfully labelled with ¹⁶¹Tb. Radiolytic decomposition of the radiolabelled compound was apparent from the radiochromatograms. Further improvement of reaction conditions is warranted in order to suppress radiolytic processes.

[en] The products of radiolysis and hydrolysis of polyacrylonitrile (PAN) in strongly alkaline conditions were studied using several methods: HRMS, FT-IR and LCMS analysis and HPLC combinations with UV/VIS and refractometry. The conditions simulate the environment formed by the cementitious materials utilized as the engineering barrier in radioactive waste disposal. Degradation products from materials such as PAN, which are part of the waste, can significantly affect the migration of the radionuclides present. The data obtained from infrared spectroscopy show the common trends: in the region of 3400-3200 cm^-1 bands are visible, which correspond to the valence N-H vibrations of the amine or amide functional group. Furthermore, bands of valence symmetric and antisymmetric CH₂ and CH₃ groups are visible in the region 2950-2850 cm^-1. The band around 2240 cm^-1 corresponds to the stretching vibrations of the nitrile group ν(C≡N). The degradation proceeds via intermediates (-C=N) and amide (-CONH₂) and leads to the formation of a carboxyl group (-COOH). Characteristic IR bands document the presence of intermediates in the reaction mixture. The presence of PAN fragments after hydrolysis was also confirmed by MS spectra

[en] This work is focused on the testing of a new ⁶⁸Ge/⁶⁸Ga radionuclide generator based on cerium dioxide in polyacrylonitrile beads. During an 18-month period, parameters of elution were monitored, and basic radiolabelling studies were carried out. As current commercial solutions deal with high elution volume and low long-term stability, the constructed system offers several improvements. The composite sorbent provides uniformity of active component dispersion and high capacity for ⁶⁸Ge. It enables minimal elution volume without fractionation (up to 1.8 mL) and stability of ⁶⁸Ge breakthrough (under 0.001%) after initial period of wash-out and low cerium leakage (under 5 ppm). (author)

[en] Two most common diglycolamides, TODGA and isoTODGA, were tested for separation of ²²¹Fr from ²²⁵Ac in preliminary studies. Diglycolamides were immobilised on polyacrylonitrile beads to form solid extractants TODGA-PAN and isoTODGA-PAN. The loading of such solid extractants was 40 %. Batch sorption experiments with both solid extractants were performed in both hydrochloric and nitric acid media in the concentration range of 0.001-8M. The weight distribution coefficients of ²²⁵Ac were determined. As expected, especially high weight distribution coefficients were achieved for both solid extractants in higher concentrations of nitric acid. Subsequently, the most promising conditions of ²²⁵Ac sorption were applied in column experiments in order to evaluate ²²¹Fr elution. The initial activity of ²²⁵Ac was 4.5 MBq and column bed volume was 0.6 ml. The yield of ²²¹Fr elution was kept over 65 % in 2.5 ml of eluate for the whole period of the long-term study. The contamination by ²²⁵Ac was kept under 1.0 % and getting lower during the time of study. To sum up, the proof of concept has been given in this preliminary study. However, in order to minimize ²²⁵Ac contamination, the parameters of proposed separation system should be optimized.

[en] Nanoparticles of α-zirconium phosphate (α-ZrP) were selected and tested as potential carriers of ²²³Ra and ²²⁵Ac. Nanoparticles of α-ZrP were prepared by the reaction of zirconium oxychloride octahydrate aqueous solution with sodium dihydrogen phosphate solution in hydrochloric acid under reflux. The prepared particles were washed by deionised water and then redispersed in ultrapure water. The size of the particles was determined using dynamic light scattering method and the Ζ-potentials were also measured. Consequently, samples were labelled in aqueous solution with ²²³Ra and ²²⁵Ac. The labelling yield exceeded 98 % in most cases both for ²²³Ra and ²²⁵Ac. Subsequently, in vitro stability studies were carried out in four biological matrices: blood serum, blood plasma, saline and 5 % albumin solution during 48 h period. Measurements of released activities revealed that samples exhibit the highest stability in saline. Released activity of ²²³Ra, ²²⁵Ac and their daughter radionuclides was around 0,5 %. On the other hand, the lowest stability was shown in blood plasma for ²²³Ra, where released activity was above 15 % and 18 % for ²¹¹Pb and ²¹¹Bi after 48 h. In blood serum was measured highest release activity for ²²⁵Ac (close to 18 %) and its daughter radionuclides ²²¹Fr (more than 20 %) and ²¹³Bi (above 32 %).

[en] In this study suitability of α-ZrP nanoparticles as a ²²³Ra and ²²⁵Ac carriers for TAT was investigated. The yields of radiolabelling were higher than 98% in both cases. Subsequently, in vitro stability studies were carried out in various biological matrices during 48 h period. Measurements of released radioactivity showed the highest stability in saline. Released activity of ²²³Ra, ²²⁵Ac and their daughter radionuclides was around 0.5%. On the other hand, the lowest stability was shown in plasma and serum. Released activity for ²²³Ra, ²²⁵Ac and their progeny atoms was from 15 to 32%. (author)

[en] Terbium-161 can be prepared as no carrier added by neutron irradiation of highly enriched gadolinium-160 target in a nuclear reactor, through indirect production route ¹⁶⁰Gd (n,γ) ¹⁶¹Gd → ¹⁶¹Tb. After irradiation,terbium must be separated from the target, typically by using cation exchange chromatography. In this work, several irradiations of highly enriched ¹⁶⁰Gd target in the form of oxide or nitrate were performed in the nuclear reactor LVR 15. For separation of ¹⁶¹Tb from target, cation exchange chromatography (Dowex 50W×8 (H+), 100-200 mesh) with variously concentrated α-hydroxyisobutyric acid as eluent was used. The presence of ¹⁶¹Tb and possible radionuclide impurities was verified by gamma spectrometry on an HPGe detector. The fractions containing ¹⁶¹Tb were purified from α-hydroxyisobutyric acid also on the cation exchange resin, using hydrochloric acid as eluent. The presence of stable impurities was verified by ICP-MS method.