Separation of 44mSc/44gSc Nuclear Isomers Based on After-Effects.

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% ß+). 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.

Determination of distribution coefficients of mercury and gold on selected extraction chromatographic resins - towards an improved separation method of mercury-197 from proton-irradiated gold targets.

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 number 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 chromatographic 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).

An alternative radiochemical separation strategy for isolation of Ac and Ra isotopes from high energy proton irradiated thorium targets for further application in Targeted Alpha Therapy (TAT).

Targeted Alpha Therapy (TAT) has shown very high potential for the treatment of cancers that were not responsive to other therapy options (e.g., ß- therapy and chemotherapy). The main constraint to the widespread use of TAT in clinics is the limited availability of alpha-emitting radionuclides. One of the most promising candidates for TAT is 225Ac (t1/2 = 9.92 days), which can be used directly in combination with selective biomolecules (e.g., antibodies, peptides, etc.) or be a generator source of 213Bi (t1/2 = 45.6 min), another shorter-lived TAT radionuclide. Several strategies are currently under investigation to increase the supply of 225Ac. One of the most attractive options is the irradiation of natural thorium-232 targets with high-energy protons (≥100 MeV). However, there are several challenges associated with this production method including the development of an efficient radiochemical purification method. During irradiation of natural thorium with proton energy above 100 MeV, several Ra isotopes (223,224,225Ra) are produced. 223Ra (t1/2 = 11.43 days) is used for the treatment of bone metastases and can also be used as a generator source for 211Pb. Additionally, 225Ra (t1/2 = 14.9 days) can be a valuable source of isotopically pure 225Ac. In the present work, we address the radiochemical separation aspects of isolating Ac and Ra isotopes from irradiated thorium targets.

Synthesis of Silver Nanoparticles Using Reactive Water-Ethanol Extracts from Murraya paniculata.

Using the radiation-chemical simulation method of free radical reactions with 2,2-diphenyl-1-picrylhydrazyl, we were able to show high antiradical activity of water-ethanol extracts from Murraya paniculata. This will allow for the creation of new bioactive antioxidants based on them. The formation of silver nanoparticles (Ag-NP) was determined using the silver-ion reduction process by M. paniculata extracts. A band of electronic plasmon resonance was identified in the optical absorption spectra of hydrosols of Ag-NP using extracts of dried M. paniculata leaves. A decrease in the number of Candida albicans and Pseudomonas aeruginosa cells after introduction into the Ag-NP system synthesized by the reduction of silver cations using M. paniculata extracts indicates their moderate antimicrobial activity.

Chemical Promiscuity of Non-Macrocyclic Multidentate Chelating Ligands for Radiometal Ions: H4neunpa-NH2 vs H4noneunpa.

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.

Potent candidates for Targeted Auger Therapy: Production and radiochemical considerations.

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.

Perturbed Angular Correlation as a Tool to Study Precursors for Radiopharmaceuticals.

One of the key components of radiopharmaceuticals for targeting imaging and therapy is a stable bifunctional chelating system to attach radionuclides to selective delivery systems. After-effects of radioactive decay can cause the release of a radioactive isotope from its chelation agent. Perturbed angular correlation (PAC) of γ-rays has become a unique technique to study the behavior of complexes formed between a chelating agent and radionuclide in vivo (in real time) over a relevant range of concentrations (10-12 M). In the present work, four radionuclides, 111In, 111mCd, and 152, 154Eu, were investigated with diethylenetriaminepentaacetic acid (DTPA) at different pH values to determine the stability constants of the complexes as well as the effects of post-decay processes, which play a major role in determining the suitability of these complexes for application as radiopharmaceuticals (e.g., in vivo generators). The study provides a convenient parameter for the characterization of radionuclide-chelator systems using the PAC method. PAC is proven to be a suitable tool to study novel chelators and radiopharmaceutical precursors attached to radiometals.

Radiation Chemical Investigation of Antioxidant Activity of Biologically Important Compounds from Plant Materials.

Radiation chemical modeling of redox reactions of biologically active compounds from plant materials showed that coumarins possess strong antiradical properties. Data confirming the radioprotective properties of these compounds were obtained. Antioxidant activity has been shown for specific medicinal plant extracts-Melilotus officinalis and Ledum palustre cormus. The radiation chemical transformations of coumarins revealed that an unsubstituted coumarin has greater radioprotective activity.

Value of syncope in patients with high-to-intermediate risk pulmonary artery embolism.

BACKGROUND: Syncope may develop in 9-35% of patients with pulmonary embolism (PE). Despite its severity and importance, the prognostic value of syncope in PE is unclear. We aimed to assess the value of syncope in patients with high-to-intermediate risk PE. METHODS: A total of 117 patients (62 males and 55 females, median age 51,86 ± 13,4 years) were enrolled into the study. According to the presence of syncope at the onset of PE, all patients were divided into two groups: the syncope group (SG) comprised 35 patients (48.8 ± 15.5 years, male 54.3%) who experienced at least one syncopal episode. The remaining 82 patients (53.4 ± 12.6 years, male 42.7%) without syncope comprised the control group (CG). RESULTS: The main predisposing risk factors of PE were the same except fewer recurrent episodes of PE (8.5 vs. 24.5% in patients from SG (p=0.048). Clinical probability of PE according to the Revised Geneva and Wells scores was high almost in every second patient in both groups (p=NS). There were twice as many patients with a high risk of fatal outcome among patients with syncope in comparison with CG patients (45.7 vs. 25.6%, respectively, p=0.032). Massive PE on computed tomography scans was found again significantly more frequently in patients with syncope (60 vs. 39%, p=0.036). The vast majority (60%) of patients with a history of syncope were treated by thrombolytic therapy (21/35) vs. only 29% of patients without syncopal events (24/82; p=0.001). In-hospital mortality was higher in patients with syncope than the control group (14.2 vs. 8.5%, p=NS). CONCLUSIONS: The history of syncope in patients with suspected PE should be considered as a possible criterion of high risk of fatal complications of in-hospital period due to frequent embolism of the pulmonary trunk and its main branches. The use of thrombolytic therapy showed a tendency in improving outcomes.