Introduction: Radiolanthanides 132La and 135La form a promising chemically matched theranostic pair. With a half-life of 18.95 h, 135La acts as the therapeutic isotope as it releases approximately 11 Auger electrons per decay, making it compatible with targeted Auger electron therapy (TAET), whereas 132La with half-life of 4.58 h undergoes positron emission making it compatible with imaging via positron emission tomography (PET). Methods: 132/135La were produced via irradiation of natural barium targets (99.9 %) with 12.8 MeV protons. A two-step separation scheme using extraction chromatographic resin TK200 (50-100 mu m) and cation exchange resin Dowex 50Wx4 (200-400 mesh) was designed. Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify non-radioactive impurities in each fraction of the separation method. The distribution coefficients of La3+ in HNO3 on the TK200 resin and on both Dowex 50Wx8 (200-400 mesh) and Dowex 50Wx4 resins in ammonium alpha-hydroxyisobutyrate (pH 4.8) were determined, respectively. Results: This novel separation scheme allowed for reliable separation of [132/135La]La3+ from the Ba2+ target material, resulting in a high radiochemical yield of 98.3 +/- 2.1 % (n = 3) with the final elute being directly compatible with subsequent radiolabeling due to the use of ammonium alpha-hydroxyisobutyrate to eliminate steps in the radiopharmaceutical synthetic process.

44gSc presents a particular interest for application in nuclear medicine for positron emission tomography (PET) due to its favorable nuclear decay properties (t1/2 = 3.97 h, Emax = 1.47 MeV, branching ratio 94.3% β+). Its nuclear isomer 44mSc (t1/2 = 58.61 h) decays by isomeric transition (IT) into 44gSc, accompanied by ≈12% of conversion electron emission, which can cause a partial release of the daughter 44gSc from the chelate complex. A 13 MeV cyclotron at TRIUMF was used to produce both 44mSc and 44gSc via the natCa(p,n)44m,gSc reaction. A 44mSc/44gSc generator was designed by using a Strata C-18E cartridge. After several tested systems, a successful separation method was developed using DOTATOC as a chelator, a Strata C-18E cartridge as a generator column, and an elution solution of 0.1 M NH4-α-HIB. The yield of the generator with the daughter 44gSc release was equal to 9.8 ± 1.0% (or ≈80% per portion of conversion). This result shows the important role of after-effects in the design of radionuclide generators. Nuclear cross-section calculations were applied using the TALYS code to allow for the determination of the most promising alternative routes for 44mSc production, which will enable the development of a full-scale 44mSc/44gSc radionuclide generator based on after-effects.

Radioisotope mercury-197g (197gHg, half-life: 64.14 h) along with its metastable isomer (197mHg, half-life: 23.8 h) are potential candidates for targeted Meitner-Auger electron therapy due to their suitable decay properties. Their production can be achieved via proton irradiation of a natural gold target, but the num-ber of studies surrounding their separation from an irradiated gold target is limited. This study focuses on the determination of distribution coefficients (Kd) of gold (III) and mercury (II) on seven extraction chro-matographic resins. Mercury Kd were measured by means of radiotracers and Inductively Coupled Plasma Mass Spectrometry (ICP_MS); values obtained from the two methods were generally in good agreement. These results can provide insight on Hg and Au chemistry and aid in the design of improved separation system(s). (c) 2022 Elsevier B.V. All rights reserved.

In recent years, radiopharmaceuticals have been increasingly used for diagnostics and treatment of cancer. In addition to a biological vector, a modern radiopharmaceutical includes a chelator that binds the radionuclide, as well as a linker for connecting the vector and the chelator. The development of such an approach requires the improvement of methods for obtaining and purifying radionuclides, and the development of methods for the synthesis of radiopharmaceuticals, i.e., preparative direction. It is also necessary to search for new vectors and chelators. This implies the development of methods for analyzing the properties of radiopharmaceuticals in general, as well as their precursors, i.e., analytical direction. In this review, we describe the prerequisites for successfully solving a wide range of challenges in these two areas of nuclear medicine at the Scientific and Experimental Department of Nuclear Spectroscopy and Radiochemistry of the Laboratory of Nuclear Problems of the Joint Institute for Nuclear Research (LNP JINR). These prerequisites are due to rich experience in obtaining the widest range of radionuclides and their application for various spectrometric studies. Both the past and present works on radiopharmaceutical topics carried out in the department are described, and ways of future development are outlined.

Introduction: Sc-44 is of great interest as a positron emission tomography (PET) radionuclide due to its suitable nuclear characteristics: E beta+max = 1.47 MeV, branching ratio 94.3% and convenient half-life of 3.97 h. Here, Sc-44 was produced via the widely used reaction Ca-44 (p,n)Sc-44 using natural calcium as a target. Methods: The irradiation was performed at TRIUMF using the 13 MeV cyclotron. The separation consisted of a combination of DGA branched resin and Dowex 50Wx8 (200-400 mesh). The distribution coefficients of Sc3+ on Dowex 50Wx8 (NH4+ form, 200-400 mesh) with ammonium alpha-hydroxyisobutyrate (pH = 4.8) medium were determined in this study. Results and conclusion: The tested scheme allows both a reliable separation of Sc-44 from the target material as well as from the other competitive metals and a final fraction with high specific activity. The achieved radiochemical yield was 95 +/- 3%. (c) 2021 Elsevier Inc. All rights reserved.

The geometry of dendritic spines has a major impact on signal transmission at excitatory synapses. To study it in detail we raised transgenic mice expressing an intrinsic green fluorescent protein-based plasma membrane marker that directly visualizes the cell surface of living neurons throughout the brain. Confocal imaging of developing hippocampal slices showed that as dendrites mature they switch from producing labile filopodia and polymorphic spine precursors to dendritic spines with morphologies similar to those reported from studies of adult brain. In images of live dendrites these mature spines are fundamentally stable structures, but retain morphological plasticity in the form of actin-rich lamellipodia at the tips of spine heads. In live mature dendrites up to 50% of spines had cup-shaped heads with prominent terminal lamellipodia whose motility produced constant alterations in the detailed geometry of the synaptic contact zone. The partial enveloping of presynaptic terminals by these cup-shaped spines coupled with rapid actin-driven changes in their shape may operate to fine-tune receptor distribution and neurotransmitter cross-talk at excitatory synapses.

To find a high purity flux for low background experiments is one of the most challenging problems. In this work, we report the production process of a highly purified ammonium acetate flux solution for low background experiments. A sub-distilled method has been used to purify initial precursors from contamination for the syntheses of final product. As a result, a high purity ammonium acetate solution was synthesized with a minimum content of elements which collectively represent the main source of background radiation (K  < 2.3 × 10–8 g/g, Th  < 2.6 × 10–11 g/g and U  < 1 × 10–11 g/g). An Estimation of the impurity content of the product has been performed with Instrumental neutron activation analysis, inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry.

A comparative investigation of two structurally related potentially nonadentate chelating ligands, H4neunpa-NH2 and H4noneunpa, has been undertaken to examine the influence of bifunctionalization on their coordination chemistry and metal ion selectivity. Significantly improved synthetic routes for each compound have been developed, employing straightforward high-yielding strategies. Radiolabeling studies with [44Sc]Sc3+, [111In]In3+, [177Lu]Lu3+, and [225Ac]Ac3+ revealed a sharp contrast between the affinity of each chelator for large radiometal ions. H4noneunpa demonstrated highly effective coordination of [177Lu]Lu3+ and [225Ac]Ac3+ achieving quantitative radiochemical yields (>98%) at ligand concentrations of 10-6 M (room temperature (RT), 10 min), with excellent stability when challenged in human serum, while H4neunpa-NH2 was unable to complex either metal ion effectively. Nuclear magnetic resonance (NMR) spectroscopy was employed to explore the coordination chemistry of each chelating ligand with nonradioactive metal ions, spanning a range of ionic radii and coordination numbers. A comprehensive conformational analysis of each metal complex was undertaken using density functional theory (DFT) calculations to explore the coordination geometries and explain the discrepancy in binding characteristics. Theoretical simulations revealed notable differences in the coordination geometry and apparent denticity of each ligand, which together account for the observed selectivity in metal binding and have important implications for the future design of complexes based upon this framework to target large radiometal ion coordination.

Targeted Auger Therapy represents great potential for the therapy of diseases which require a high degree of selectivity on the cellular level (e.g. for therapy of metastatic cancers). Due to their high Linear Energy Transfer (LET), Auger emitters, combined with selective biological systems which enable delivery of radionuclides close to the DNA of the targeting cell, can be extremely selective and powerful treatment tools. There are two main aspects associated with the development of efficient radiopharmaceuticals based on Auger Emitters: a) the availability of suitable Auger-emitting radionuclides for therapy and b) the design of targeting vectors which can deliver Auger emitters into/close to the nucleus. In the present review, we address the first aspect by defining important parameters for the selection of radionuclides for application to Targeted Auger Therapy and form a categorized list of the most promising radionuclides, their possible production routes, and their use in the synthesis of radiopharmaceuticals.

A method for the production of 111 In from an antimony target irradiated with 600 MeV protons has been developed. Here, a three-stage scheme of indium purification using ion-exchange chromatography is performed. The radiochemical yield is 85%, with a decontamination factor of the target material of no less than 10 9 . The 111 In preparation produced by the present method was used in studies of perturbed angular correlations. Also, a procedure for the production and separation of 117 m Sn/ 119 m Te was developed, which is of particular interest for further studies on designing a generator to produce 119 Sb.

Targeted radionuclide therapy (TRT) and diagnostics are currently the most intensively developing fields of nuclear medicine as they allow for very precise imaging of tumors (or other targeted tissue), and minimization of healthy tissue damage during medical therapy. TRT relies on the labeling of a radionuclide to a targeting vector – a biomolecule that has high affinity to over-expressed antigens on the surface of tumor cells. It targets tumors, or other diseases, at the cellular level and increases the radiation dose to the target relative to healthy tissue during therapy. However, design and synthesis of radiopharmaceuticals suitable for TRT require a solid understanding of the stability of radionuclide complexes in vivo. Conventional methods to characterize thermodynamic stability of complexes often rely on non-radioactive surrogates under biologically irrelevant conditions; moreover, little information on kinetics of formation and kinetic inertness can be drawn. Therefore, in this proposal we request 15 shifts to pursue our work on determining the kinetics of complex formation (and stability) for In/Cd, Sb, Pb and Hg based ligands and the study of in vivo radionuclide generators utilizing pairs of lanthanides with the use of Perturbed Angular Correlation of γ-rays (PAC) spectroscopy. Requested shifts: 15 shifts (Cd, Sb, Nd, La, Gd, Gd, Tb, Lu, Hg, Pb), split into several runs over 2 years.