BACKGROUND: Radioligand therapy using alpha emitters has gained more and more prominence in the last decade. Despite continued efforts to identify new appropriate radionuclides, the combination of 225Ac/213Bi remains among the most promising. Bismuth-213 has been employed in clinical trials in combination with appropriate vectors to treat patients with various forms of cancer, such as leukaemia, bladder cancer, neuroendocrine tumours, melanomas, gliomas, or lymphomas. However, the half-life of 213Bi (T½ = 46 min) implies that its availability for clinical use is limited to hospitals possessing a 225Ac/213Bi radionuclide generator, which is still predominantly scarce. We investigated a new Ac/Bi generator system based on using the composite sorbent α-ZrP-PAN (zirconium(IV) phosphate as active component and polyacrylonitrile as matrix). The developed 225Ac/213Bi generator was subjected to long-term testing after its development. The elution profile was determined and the elution yield, the contamination of the eluate with the parent 225Ac and the contamination of the eluate with the column material were monitored over time. RESULTS: The high activity (75 MBq of parent 225Ac) generator with a length of 75 mm and a diameter of 4 mm containing the composite sorbent α-ZrP-PAN with a particle size of 0.8 to 1.0 mm as the stationary phase, eluted with a mixture of 10 mM DTPA in 5 mM nitric acid, provided 213Bi with yields ranging from 77 % to 96 % in 2.8 mL of eluate, with parent 225Ac contamination in the order of 10-3 %, up to twenty days of use. CONCLUSION: All the results of the monitored parameters indicate that the composite sorbent α-ZrP-PAN based separation system for the elution of 213Bi is a very promising and functional solution.

• Klíčová slova
• Actinium-225, Bismuth-213, Diethylenetriaminepentaacetic acid, Ion exchange, Zirconium phosphate,
• MeSH
• aktinium * chemie   MeSH
• alfa částice * terapeutické užití   MeSH
• bismut * chemie   MeSH
• radiochemie metody   přístrojové vybavení   MeSH
• radioisotopové generátory MeSH
• radionuklidy * chemie   MeSH
• zirkonium chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Actinium-225 MeSH Prohlížeč
• aktinium * MeSH
• bismut * MeSH
• Bismuth-213 MeSH Prohlížeč
• radionuklidy * MeSH
• zirkonium MeSH

Zirconium phosphate (ZrP), especially its alpha allotropic modification, appears to be a very promising sorbent material for the sorption and separation of various radionuclides due to its properties such as an extremely high ion exchange capacity and good radiation stability. Actinium-225 and its daughter nuclide 213Bi are alpha emitting radioisotopes of high interest for application in targeted alpha therapy of cancer. Thus, the main aim of this paper is to study the sorption of 225Ac on the α-ZrP surface and its kinetics, while the kinetics of the sorption is studied using natEu as a non-radioactive homologue of 225Ac. The sorption properties of α-ZrP were tested in an acidic environment (hydrochloric and nitric acid) using batch sorption experiments and characterized using equilibrium weight distribution coefficients Dw (mL/g). The modeling of the experimental data shows that the kinetics of 225Ac sorption on the surface of α-ZrP can be described using a film diffusion model (FD). The equilibrium weight distribution coefficient Dw for 225Ac in both hydrochloric and nitric acid reached the highest values in the concentration range 5.0-7.5 mM (14,303 ± 153 and 65,272 ± 612 mL/g, respectively). Considering the results obtained in radioactive static sorption experiments with 225Ac and in non-radioactive kinetic experiments with natEu, α-ZrP seems to be a very promising material for further construction of a 225Ac/213Bi generator.

• Klíčová slova
• actinium-225, bismuth-213, kinetics, phosphate, sorption, zirconium,
• Publikační typ
• časopisecké články MeSH

Nanoparticles of various materials were proposed as carriers of nuclides in targeted alpha particle therapy to at least partially eliminate the nuclear recoil effect causing the unwanted release of radioactive progeny originating in nuclear decay series of so-called in vivo generators. Here, we report on the study of 211Pb and 211Bi recoils release from the 223Ra surface-labelled TiO2 nanoparticles in the concentration range of 0.01-1 mg/mL using two phase separation methods different in their kinetics in order to test the ability of progeny resorption. We have found significant differences between the centrifugation and the dialysis used for labelled NPs separation as well as that the release of 211Pb and 211Bi from the nanoparticles also depends on the NPs dispersion concentration. These findings support our previously proposed recoils-retaining mechanism of the progeny by their resorption on the NPs surface. At the 24 h time-point, the highest overall released progeny fractions were observed using centrifugation (4.0% and 13.5% for 211Pb and 211Bi, respectively) at 0.01 mg/mL TiO2 concentration. The lowest overall released fractions at the 24 h time-point (1.5% and 2.5% for 211Pb and 211Bi respectively) were observed using dialysis at 1 mg/mL TiO2 concentration. Our findings also indicate that the in vitro stability tests of such radionuclide systems designed to retain recoil-progeny may end up with biased results and particular care needs to be given to in vitro stability test experimental setup to mimic in vivo dynamic conditions. On the other hand, controlled and well-defined progeny release may enhance the alpha-emitter radiation therapy of some tumours.

• Klíčová slova
• Bi-213, Bismuth, Pb-211, Ra-223, Radium, TiO2, lead, nanoparticles, nuclear recoil,
• Publikační typ
• časopisecké články MeSH

This review summarizes recent progress and developments as well as the most important pitfalls in targeted alpha-particle therapy, covering single alpha-particle emitters as well as in vivo alpha-particle generators. It discusses the production of radionuclides like 211At, 223Ra, 225Ac/213Bi, labelling and delivery employing various targeting vectors (small molecules, chelators for alpha-emitting nuclides and their biomolecular targets as well as nanocarriers), general radiopharmaceutical issues, preclinical studies, and clinical trials including the possibilities of therapy prognosis and follow-up imaging. Special attention is given to the nuclear recoil effect and its impacts on the possible use of alpha emitters for cancer treatment, proper dose estimation, and labelling chemistry. The most recent and important achievements in the development of alpha emitters carrying vectors for preclinical and clinical use are highlighted along with an outlook for future developments.

• Klíčová slova
• 223Ra, actinium, alpha particle, astatine, bismuth, decay, in vivo generators, nuclear recoil, radium, targeted alpha therapy,
• MeSH
• aktinium chemie   terapeutické užití   MeSH
• alfa částice terapeutické užití   MeSH
• astat chemie   terapeutické užití   MeSH
• bismut chemie   terapeutické užití   MeSH
• chelátory chemie   farmakokinetika   MeSH
• dávka záření MeSH
• heterocyklické sloučeniny monocyklické chemie   farmakokinetika   MeSH
• heterocyklické sloučeniny chemie   farmakokinetika   MeSH
• knihovny malých molekul chemie   farmakokinetika   MeSH
• lidé MeSH
• nádory patologie   radioterapie   MeSH
• nosiče léků aplikace a dávkování   chemie   MeSH
• radiofarmaka chemie   terapeutické užití   MeSH
• radionuklidy chemie   terapeutické užití   MeSH
• radium chemie   terapeutické užití   MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• 1,4,7-triazacyclononane-N,N',N''-triacetic acid MeSH Prohlížeč
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid MeSH Prohlížeč
• Actinium-225 MeSH Prohlížeč
• aktinium MeSH
• astat MeSH
• Astatine-211 MeSH Prohlížeč
• bismut MeSH
• Bismuth-213 MeSH Prohlížeč
• chelátory MeSH
• heterocyklické sloučeniny monocyklické MeSH
• heterocyklické sloučeniny MeSH
• knihovny malých molekul MeSH
• nosiče léků MeSH
• radiofarmaka MeSH
• radionuklidy MeSH
• Radium-223 MeSH Prohlížeč
• radium MeSH

BACKGROUND: Targeted alpha therapy (TAT) is an effective option for cancer treatment. To maximize its efficacy and minimize side effects, carriers must deliver radionuclides to target tissues. Most of the nuclides used in TAT decay via the alpha cascade, producing several radioactive daughter nuclei with sufficient energy to escape from the original carrier. Therefore, studying these daughter atoms is crucial in the search for new carriers. Nanoparticles have potential as carriers due to their structure, which can prevent the escape of daughter atoms and reduce radiation exposure to non-target tissues. This work focuses on determining the released activity of 221Fr and 213Bi resulting from the decay of 225Ac labelled TiO2 nanoparticles. RESULTS: Labelling of TiO2 nanoparticles has shown high sorption rates of 225Ac and its progeny, 221Fr and 213Bi, with over 92 % of activities sorbed on the nanoparticle surface for all measured radionuclides. However, in the quasi-dynamic in vitro system, the released activity of 221Fr and 213Bi is strongly dependent on the nanoparticles concentration, ranging from 15 % for a concentration of 1 mg/mL to approximately 50 % for a nanoparticle concentration of 10 μg/mL in saline solution. The released activities of 213Bi were lower, with a maximum value of around 20 % for concentrations of 0.05, 0.025, and 0.01 mg/mL. The leakage of 225Ac and its progeny was tested in various biological matrices. Minimal released activity was measured in saline at around 10 % after 48 h, while the maximum activity was measured in blood serum and plasma at 20 %. The amount of 225Ac released into the media was minimal (<3 %). The in vitro results were confirmed in a healthy mouse model. The difference in %ID/g was clearly visible immediately after dissection and again after 6 h when 213Bi reached equilibrium with 225Ac. CONCLUSION: The study verified the potential release of 225Ac progeny from the labelled TiO2 nanoparticles. Experiments were performed to determine the dependence of released activity on nanoparticle concentration and the biological environment. The results demonstrated the high stability of the prepared 225Ac@TiO2 NPs and the potential release of progeny over time. In vivo studies confirmed our hypothesis. The data obtained suggest that the daughter atoms can escape from the original carrier and follow their own biological pathways in the organism.

• Klíčová slova
• Actinium-225, Bismuth-213, Nanoparticles, Targeted alpha therapy, TiO(2),
• MeSH
• aktinium * chemie   MeSH
• izotopové značení MeSH
• myši MeSH
• nanočástice * chemie   MeSH
• radionuklidy * chemie   MeSH
• titan * chemie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Actinium-225 MeSH Prohlížeč
• aktinium * MeSH
• radionuklidy * MeSH
• titan * MeSH
• titanium dioxide MeSH Prohlížeč