Patients with gastrointestinal bleeding (GIB) exhibit varying tolerances to acute blood loss. We aimed to investigate the effect of relative Hb decrease (ΔHb%) on GIB outcomes. Participants enrolled in the Hungarian GIB Registry between 2019 and 2022 were analyzed.
View Article and Find Full Text PDFRadioisotopes of fluorine (F), scandium (Sc, Sc), lutetium (Lu), and yttrium (Y, Y) have decay properties ideally suited for targeted nuclear imaging and therapy with small biologics, such as peptides and antibody fragments. However, a single-molecule strategy to introduce these radionuclides into radiopharmaceuticals under mild conditions to afford inert in vivo complexes is critically lacking. Here, we introduce HL2 and HL3, two small-cavity macrocyclic chelator structural isomers bearing a single phosphonate functional group.
View Article and Find Full Text PDFWe present a detailed investigation of the coordination chemistry toward [Cu/Cu]copper of a series of HDEDPA derivatives (HDEDPA = 6,6'-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid) containing cyclohexyl (HCHXDEDPA), cyclopentyl (HCpDEDPA) or cyclobutyl (HCBuDEDPA) spacers. Furthermore, we also developed a strategy that allowed the synthesis of a HCBuDEDPA analogue containing an additional NHBoc group at the cyclobutyl ring, which can be used for conjugation to targeting units. The X-ray structures of the Cu(II) complexes evidence distorted octahedral coordination around the metal ion in all cases.
View Article and Find Full Text PDFThe widely established PET isotope F does not have a therapeutic partner. We have recently established that the Sc-F bond can be formed under aqueous, high yielding conditions, paving the way to providing F as diagnostic partners to Sc and Lu radiotherapeutics. Here, we synthesized a library of tacn-based chelators comprised of 10 structurally unique permutations incorporating acetate, methyl-benzylamide and picolinate donor arms.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
The elementally matched Co (t=17.53 h, I=77 %)/Co (t=9.10 h, internal conversion=100 %) radioisotope pair is of interest for development of paired diagnostic/therapeutic radiopharmaceuticals.
View Article and Find Full Text PDFIn 1965, Jack Edmonds characterized pairs of graphs and with a bijection between their edge sets that form a pair of dual graphs realizing the vertices and countries of a map embedded in a surface. A necessary condition is that, if = (d, …, d) and = (t,…, t) denote the degree sequences of two such graphs, then , where is the number of edges in each of the two graphs and is the Euler characteristic of the surface. However, this condition is not sufficient, and it is an open question to characterize bi-vectors () that are , that is, that can be realized as the degree sequences of pairs and of surface-embedded graphs.
View Article and Find Full Text PDFBiallelic loss-of-function variants in the IYD gene cause hypothyroidism resulting from iodine wasting. We describe 8 patients (from 4 families in which the parents are first cousins) who are homozygous for a variant in IYD (including a novel missense deleterious variant, c.791C>T [P264L], in 1 family).
View Article and Find Full Text PDFIntroduction: Craniopharyngiomas (CPs) are benign brain tumors accounting for 5 - 11% of intracranial tumors in children. These tumors often recur and can cause severe morbidity. Postoperative radiotherapy efficiently controls and prevents progression and recurrence.
View Article and Find Full Text PDFNuclear medicine harnesses radioisotopes for the diagnosis and treatment of disease. While the isotopes Tc and In have enabled the clinical diagnosis of millions of patients over the past 3 decades, more recent clinical translation of numerous Ga/Lu-based radiopharmaceuticals for diagnostic imaging and therapy underscores the clinical utility of metal-based radiopharmaceuticals in mainstream cancer treatment. In addition to such established radionuclides, advancements in radioisotope production have enabled the production of radionuclides with a broad range of half-lives and emission properties of interest for nuclear medicine.
View Article and Find Full Text PDFTo harness radiometals in clinical settings, a chelator forming a stable complex with the metal of interest and targets the desired pathological site is needed. Toward this goal, we previously reported a unique set of chelators that can stably bind to both large and small metal ions, via a conformational switch. Within this chelator class, py-macrodipa is particularly promising based on its ability to stably bind several medicinally valuable radiometals including large La, Bi, and small Sc.
View Article and Find Full Text PDFThe development of inert, biocompatible chelation methods is required to harness the emerging positron emitting radionuclide Ti for radiopharmaceutical applications. Herein, we evaluate the Ti-coordination chemistry of four catechol-based, hexacoordinate chelators using synthetic, structural, computational, and radiochemical approaches. The siderophore enterobactin (Ent) and its synthetic mimic TREN-CAM readily form mononuclear Ti species in aqueous solution at neutral pH.
View Article and Find Full Text PDFIntroduction A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al.
View Article and Find Full Text PDFRecent Food and Drug Administration (FDA) approval of diagnostic and therapeutic radiopharmaceuticals and concurrent miniaturization of particle accelerators leading to improved access has fueled interest in the development of chemical transformations suitable for short-lived radioactive isotopes on the tracer scale. This recent renaissance of radiochemistry is paired with new opportunities to study fundamental chemical behavior and reactivity of elements to improve their production, separation, and incorporation into bioactive molecules to generate new radiopharmaceuticals. This outlook outlines pertinent challenges in the field of radiochemistry and indicates areas of opportunity for chemical discovery and development, including those of clinically established (C-11, F-18) and experimental radionuclides in preclinical development across the periodic table.
View Article and Find Full Text PDFThis study is the first attempt to find a relation between the opportunistic observation data of an easily identifiable but locally rare bird, in our case the lesser black-backed gull (), and the Corine Land Cover habitat map by applying a resource selection function model to reveal the habitat selection of the species. We provide a scientific analysis using the valuable citizen science dataset sourced from the www.birding.
View Article and Find Full Text PDFDiscrete luminescent lanthanide complexes represent a potential alternative to organic chromophores due to their tunability of optical properties, insensitivity to photobleaching, and large pseudo-Stokes shifts. Previously, we demonstrated that the lack of depth penetration of UV excitation required to sensitize discrete terbium and europium complexes can be overcome using Cherenkov radiation emitted by clinically employed radioisotopes in situ. Here, we show that the second-generation europium complexes [Eu(pcta-PEPA)] and [Eu(tacn-pic-PEPA)] (Φ = 57% and 76%, respectively) lower the limit of detection (LoD) to 1 nmol in the presence of 10 μCi of Cherenkov emitting isotopes, F and Ga.
View Article and Find Full Text PDFWe synthesized, thanks to the regiospecific -functionalization using an orthoamide intermediate, two 1,4,7-triazacyclononane derivatives containing an acetate arm and either a methylpyridine or a picolinic acid group, respectively, H and H, as new Ga chelators for potential use in nuclear medicine. The corresponding Ga complexes were synthesized and structurally characterized in solution by H and C NMR. The [Ga()] complex appears to exist in solution as two diasteroisomeric pairs of enantiomers, as confirmed by density functional theory (DFT) calculations, while for [Ga()], a single species is present in solution.
View Article and Find Full Text PDFUntil November 2019 in Belgium, dried blood spot (DBS) sampling was performed between 72 and 120 hours of life, when a majority of newborns had already been discharged from the maternity. In November 2019, the policy for newborn screening in South Belgium changed to allow sampling as soon as 48 hours of life, with the objective to accelerate the process and to allow more sampling during the hospital stay. Our objective was to evaluate the impact of this policy modification and, in particular, to assess the effectiveness of screening for hypothyroidism based on sampling before or after 72 hours of life, as well as to compare the effectiveness of DBS collection before discharge or at home.
View Article and Find Full Text PDFThe solution chemistry of the hydrolytic, early-transition-metal ions Ti and Sc represents a coordination chemistry challenge with important real-world implications, specifically in the context of Ti/Sc and Ti/Sc radiochemical separations. Unclear speciation of the solid and solution phases and tertiary mixtures of mineral acid, organic chelators, and solid supports are common confounds, necessitating tedious screening of multiple variables. Herein we describe how thermodynamic speciation data in solution informs the design of new solid-phase chelation approaches enabling separations of Ti and Sc.
View Article and Find Full Text PDFActivation of metalloprodrugs or prodrug activation using transition metal catalysts represents emerging strategies for drug development; however, they are frequently hampered by poor spatiotemporal control and limited catalytic turnover. Here, we demonstrate that metal complex-mediated, autolytic release of active metallodrugs can be successfully employed to prepare clinical grade (radio-)pharmaceuticals. Optimization of the Lewis-acidic metal ion, chelate, amino acid linker, and biological targeting vector provides means to release peptide-based (radio-)metallopharmaceuticals in solution and from the solid phase using metal-mediated, autolytic amide bond cleavage (MMAAC).
View Article and Find Full Text PDFChlorotoxin (CTX), a scorpion venom-derived 36-residue miniprotein, binds to and is taken up selectively by glioblastoma cells. Previous studies provided controversial results concerning target protein(s) of CTX. These included CLC3 chloride channel, matrix metalloproteinase 2 (MMP-2), regulators of MMP-2, annexin A2, and neuropilin 1 (NRP1).
View Article and Find Full Text PDFThe genus belongs to the family (order , phylum ) and harbours aerobic chemoheterotrophic bacteria. Members of this genus were isolated from various aquatic habitats, and our analysis based on global amplicon sequencing data revealed that their relative abundance can reach up to 5-10 % of the bacterioplankton in soda lakes and pans. Although a remarkable fraction of the most frequent genotypes that we identified from continental aquatic habitats is still uncultured, five new alkaliphilic strains were characterized in detail in this study, which were isolated from three different soda lakes and pans of the Carpathian Basin (Hungary).
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