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

In this study it is developed a model for the detailed and automatic study of the alpha-particle spectra coming from detection systems. The fitting of a typical shape of the alpha peak is performed by a Gaussian function for the right side of the peak and a sum of two Gaussian functions for its left tail. The model takes into account the entire spectrum background and, particular attention is posed to the analysis of overlapped peaks, background noise and peaks with low statistic counting. The effectiveness of the proposed model is supported by several tests.

• Klíčová slova
• Alpha-particle spectrometry, Peak shape function, Spectral deconvolution, Spectrum analysis,
• Publikační typ
• časopisecké články MeSH

Energy deposition clusters in the nanometer scale have been investigated systematically in electron, proton, and alpha-particle tracks. The mean absolute frequency distributions of ionization clusters in nanometer sites have been computed. For locally multiply damaged sites and especially for double-strand breaks, the threshold numbers of ionizations in a site of a given diameter necessary for their induction have been estimated. At least three to six ionizations localized in sites of 1 to 4 nm diameter, respectively, are required to produce the double-strand break.

• MeSH
• alfa částice * MeSH
• částice - urychlovače * MeSH
• elektrony * MeSH
• jaderná energie * MeSH
• protony * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protony * MeSH

Targeted alpha therapy with radionuclides undergoing multiple alpha-particle decays is a promising method of nuclear medicine. To study the effectiveness of alpha versus beta emitters, survival of DU145 prostate cancer cells exposed to 223Ra or 177Lu was assessed. Per decay, the cells were much more sensitive to the alpha than beta emitter. However, per unit dose the sensitivities would be comparable, contrary to the well-known evidence, if the decay energy were deposited within the sample completely and homogeneously. Measurements by Timepix detectors showed about three times higher counts of alpha particles above than below the sample. After the first alpha decay of 223Ra to 219Rn, this gas likely moves upwards and its subsequent three alpha decays occur in the upper part of the sample. Correct estimation of absorbed dose is a critical issue when analysing in vitro data and when translating their results to clinical applications.

• MeSH
• alfa částice terapeutické užití   MeSH
• lidé MeSH
• radiometrie metody   MeSH
• radionuklidy terapeutické užití   MeSH
• radium * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• radionuklidy MeSH
• Radium-223 MeSH Prohlížeč
• radium * MeSH

The importance of fluorescence light microscopy for understanding cellular and sub-cellular structures and functions is undeniable. However, the resolution is limited by light diffraction (~200-250 nm laterally, ~500-700 nm axially). Meanwhile, super-resolution microscopy, such as structured illumination microscopy (SIM), is being applied more and more to overcome this restriction. Instead, super-resolution by stimulated emission depletion (STED) microscopy achieving a resolution of ~50 nm laterally and ~130 nm axially has not yet frequently been applied in plant cell research due to the required specific sample preparation and stable dye staining. Single-molecule localization microscopy (SMLM) including photoactivated localization microscopy (PALM) has not yet been widely used, although this nanoscopic technique allows even the detection of single molecules. In this study, we compared protein imaging within metaphase chromosomes of barley via conventional wide-field and confocal microscopy, and the sub-diffraction methods SIM, STED, and SMLM. The chromosomes were labeled by DAPI (4',6-diamidino-2-phenylindol), a DNA-specific dye, and with antibodies against topoisomerase IIα (Topo II), a protein important for correct chromatin condensation. Compared to the diffraction-limited methods, the combination of the three different super-resolution imaging techniques delivered tremendous additional insights into the plant chromosome architecture through the achieved increased resolution.

• Klíčová slova
• Hordeum vulgare, chromatin, deconvolution microscopy, metaphase chromosome, nanoscopy, photoactivated localization microscopy, stimulated emission depletion microscopy, structured illumination microscopy, topoisomerase II, wide-field microscopy,
• MeSH
• chromozomy rostlin chemie   genetika   metabolismus   MeSH
• DNA-topoisomerasy typu II metabolismus   MeSH
• fluorescenční barviva chemie   MeSH
• fluorescenční mikroskopie metody   MeSH
• indoly chemie   MeSH
• ječmen (rod) cytologie   genetika   MeSH
• konfokální mikroskopie metody   MeSH
• metafáze genetika   MeSH
• reprodukovatelnost výsledků MeSH
• zobrazení jednotlivé molekuly metody   MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• DAPI MeSH Prohlížeč
• DNA-topoisomerasy typu II MeSH
• fluorescenční barviva MeSH
• indoly MeSH

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.

• Klíčová slova
• BSH, alpha-particle, cancer cell killing, chromosome aberrations, proton-boron (B) fusion-enhanced proton therapy (PBFEPT), protontherapy,
• Publikační typ
• časopisecké články MeSH

Bacteriophages are ubiquitous in nature and represent a vast repository of genetic diversity, which is driven by the endless coevolution cycle with a diversified group of bacterial hosts. Studying phage-host interactions is important to gain novel insights into their dynamic adaptation. In this study, we isolated 12 phages infecting species of the Acinetobacter baumannii-Acinetobacter calcoaceticus complex which exhibited a narrow host range and similar morphological features (podoviruses with short tails of 9-12 nm and isometric heads of 50-60 nm). Notably, the alignment of the newly sequenced phage genomes (40-41 kb of DNA length) and all Acinetobacter podoviruses deposited in Genbank has shown high synteny, regardless of the date and source of isolation that spans from America to Europe and Asia. Interestingly, the C-terminal pectate lyase domain of these phage tail fibres is often the only difference found among these viral genomes, demonstrating a very specific genomic variation during the course of their evolution. We proved that the pectate lyase domain is responsible for phage depolymerase activity and binding to specific Acinetobacter bacterial capsules. We discuss how this mechanism of phage-host co-evolution impacts the tail specificity apparatus of Acinetobacter podoviruses.

• MeSH
• Acinetobacter baumannii virologie   MeSH
• Acinetobacter calcoaceticus virologie   MeSH
• genom virový genetika   MeSH
• hostitelská specificita fyziologie   MeSH
• Podoviridae klasifikace   genetika   metabolismus   MeSH
• polygalakturonasa metabolismus   MeSH
• polysacharid-lyasy metabolismus   MeSH
• proteinové domény fyziologie   MeSH
• sekvence nukleotidů MeSH
• virion genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH
• Názvy látek
• pectate lyase MeSH Prohlížeč
• polygalakturonasa MeSH
• polysacharid-lyasy MeSH

Electron and confocal microscopy were used to observe the entry and the movement of polyomavirus virions and artificial virus-like particles (VP1 pseudocapsids) in mouse fibroblasts and epithelial cells. No visible differences in adsorption and internalization of virions and VP1 pseudocapsids ("empty" or containing DNA) were observed. Viral particles entered cells internalized in smooth monopinocytic vesicles, often in the proximity of larger, caveola-like invaginations. Both "empty" vesicles derived from caveolae and vesicles containing viral particles were stained with the anti-caveolin-1 antibody, and the two types of vesicles often fused in the cytoplasm. Colocalization of VP1 with caveolin-1 was observed during viral particle movement from the plasma membrane throughout the cytoplasm to the perinuclear area. Empty vesicles and vesicles with viral particles moved predominantly along microfilaments. Particle movement was accompanied by transient disorganization of actin stress fibers. Microfilaments decorated by the VP1 immunofluorescent signal could be seen as concentric curves, apparently along membrane structures that probably represent endoplasmic reticulum. Colocalization of VP1 with tubulin was mostly observed in areas close to the cell nuclei and on mitotic tubulin structures. By 3 h postinfection, a strong signal of the VP1 (but no viral particles) had accumulated in the proximity of nuclei, around the outer nuclear membrane. However, the vast majority of VP1 pseudocapsids did not enter the nuclei.

• MeSH
• adsorpce MeSH
• beta-cyklodextriny * MeSH
• biologický transport MeSH
• buněčné jádro metabolismus   virologie   MeSH
• buněčné linie MeSH
• cyklodextriny farmakologie   MeSH
• kapsida analýza   metabolismus   MeSH
• kaveolin 1 MeSH
• kaveoliny fyziologie   MeSH
• kaveoly fyziologie   MeSH
• myši MeSH
• Polyomavirus fyziologie   MeSH
• tubulin analýza   MeSH
• virion fyziologie   MeSH
• virové plášťové proteiny * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• beta-cyklodextriny * MeSH
• Cav1 protein, mouse MeSH Prohlížeč
• cyklodextriny MeSH
• kaveolin 1 MeSH
• kaveoliny MeSH
• methyl-beta-cyclodextrin MeSH Prohlížeč
• tubulin MeSH
• virové plášťové proteiny * MeSH
• VP1 protein, polyomavirus MeSH Prohlížeč

The crystals of (Lu,Gd)3(Ga,Al)5O12 multicomponent garnets with high density ρ and effective atomic number Zeff are characterized by high scintillation efficiency and a light yield value up to 50,000 ph/MeV. During recent years, single-crystalline films and composite film/crystal scintillators were developed on the basis of these multicomponent garnets. These film/crystal composites are potentially applicable for particle identification by pulse shape discrimination due to the fact that α-particles excite only the film response, γ-radiation excites only the substrate response, and β-particles excite both to some extent. Here, we present new results regarding scintillating properties of selected (Lu,Gd)3(Ga,Al)5O12:Ce single-crystalline films under excitation by alpha and beta particles and gamma ray photons. We conclude that some of studied compositions are indeed suitable for testing in the proposed application, most notably Lu1.5Gd1.5Al3Ga2O12:Ce film on the GAGG:Ce substrate, exhibiting an α-particle-excited light yield of 1790-2720 ph/MeV and significantly different decay curves excited by α- and γ-radiation.

• Klíčová slova
• Ce3+-doped multicomponent garnets, alpha and beta particles, gamma ray, liquid-phase epitaxy, scintillation, single-crystalline films,
• Publikační typ
• časopisecké články MeSH

The reduction of analysis time, cost, and improvement of separation efficiency are the main requirements in the development of high-throughput assay methods in bioanalysis. It can be achieved either by ultra-high-performance liquid chromatography (UHPLC) using stationary phases with small particles (<2 μm) at high back pressures or by using opposite direction--monolithic stationary phases with low back pressures. The application of new types of monolithic stationary phases for UHPLC is a novel idea combining these two different paths. The aim of this work was to test the recently introduced second-generation of monolithic column Chromolith® HighResolution for UHPLC analysis of liposoluble vitamins in comparison with core-shell and fully porous sub-2 μm columns with different particle sizes, column lengths, and shapes. The separation efficiency, peak shape, resolution, time of analysis, consumption of mobile phase, and lifetime of columns were calculated and compared. The main purpose of the study was to find a new, not only economical option of separation of liposoluble vitamins for routine practice.

• Klíčová slova
• Bioanalysis, Core-shell, High-resolution monolith, LC, Liposoluble vitamins,
• MeSH
• alfa-tokoferol analýza   krev   MeSH
• lidé MeSH
• mateřské mléko chemie   MeSH
• poréznost MeSH
• syntetické pryskyřice chemie   MeSH
• velikost částic MeSH
• vitamin A analýza   krev   MeSH
• vysokoúčinná kapalinová chromatografie přístrojové vybavení   metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• alfa-tokoferol MeSH
• syntetické pryskyřice MeSH
• vitamin A MeSH