Photonuclear Alchemy: Obtaining Medical Isotopes of Gold from Mercury Irradiated on Electron Accelerators

In our work, the photonuclear production of 198,199Au isotopes for nuclear medicine purposes was studied, and a method for their recovery from irradiated mercury was developed. The yields of the corresponding nuclear reactions were determined, and a comparison of various methods of obtaining gold radioisotopes was provided. New sorbents based on benzo-15-crown-5, which selectively binds gold, were studied, and the optimal conditions for Au recovery with a high degree of purification from mercury were found. It was established that, for the fast and quantitative recovery of Au isotopes, it was necessary to add at least 0.1 mg of the carrier. As a result, the developed method can be regularly used to obtain 198,199Au for the research of radiopharmaceuticals based on them

Carbon Nanomaterials for Sorption of 68Ga for Potential Using in Positron Emission Tomography

In present work, carbon nanomaterials (CNMs) are investigated as potential carriers of 68Ga, which is widely used in positron emission tomography (PET) in nuclear medicine. Sorption behavior of 68Ga was studied onto CNMs of various structures and chemical compositions: nanodiamonds (ND), reduced graphite oxide (rGiO) and multi-walled carbon nanotubes (MWCNT), as well as their oxidized (ND–COOH) or reduced (rGiO–H, MWCNT–H) forms. The physicochemical properties of the nanoparticles were determined by high resolution transmission electron microscopy, x-ray photoelectron spectroscopy, dynamic light scattering and potentiometric titration. The content of 68Ga in the solutions during the study of sorption was determined by gamma-ray spectrometry. The highest degree of 68Ga sorption was observed on ND and ND–COOH samples, and the optimal sorption conditions were determined: an aqueous solution with a pH of 5–7, m/V ratio of 50 μg/mL and a room temperature (25 °C). The 68Ga@ND and 68Ga@ND–COOH conjugates were found to be stable in a model blood solution—phosphate-buffered saline with a pH of 7.3, containing 40 g/L of bovine serum albumin: 68Ga desorption from these samples in 90 minutes was no more than 20% at 25 °C and up to 30% at 37 °C. Such a quantity of desorbed 68Ga does not harm the body and does not interfere with the PET imaging process. Thus, ND and ND–COOH are promising CNMs for using as carriers of 68Ga for PET diagnostics

Biogeochemical processes at the Krasniy Yar seepage area (Lake Baikal) and a comparison with oceanic seeps

The expulsion of sedimentary, methane-rich fluids to bottom waters is a widespread process in Lake Baikal (eastern Siberia), resulting in deep water cold seep systems comparable in size and frequency to those of oceanic, high-productivity continental margins. Little is known, however, about how biogeochemical processes in Baikal cold seeps compare with those of oceanic cold seeps. In this paper, we present new pore water chemistry data from the Krasniy Yar seepage area located on the slope near the Selenga river delta. We compare biogeochemical processes deduced from these pore water chemical profiles with processes prevalent at oceanic cold seeps of highly productive continental margins. This comparison allows to draw the following conclusions: (1) in sediments not affected by seepage the fresh water mass of Lake Baikal results in a very low relative importance of the nitrogenous and sulfidic geochemical zones compared to the ocean; (2) diagenetic processes involving silicate minerals are, however, similar in Lake Baikal and the ocean; (3) fluid advection rates in cold seep sediments are similar in Lake Baikal and ocean systems but (4) the deep methane flux of Baikal seeps is mitigated by reaction with O-2, and possibly Mn(IV) and Fe(III) oxides, whereas in oceanic sediments the main methane-consuming process is the anaerobic oxidation of methane with sulfate. Lake Baikal cold seep sediments are therefore nearly devoid of authigenic carbonate minerals and have a reduced capacity to decrease the deep methane flux

Tritium Labeling and Phase Distribution of 18-Crown-6 and Its Derivatives for Further Reprocessing of Radium Waste

To date, the world has accumulated a large amount of long-lived radioactive materials that need to be disposed of or reprocessed. Such materials include nuclear legacy objects containing 226Ra, which is an important material for obtaining a wide range of isotopes for nuclear medicine via irradiation in reactors, cyclotrons, and electron accelerators. For the selective recovery of 226Ra from waste materials, crown-ether (CE) 18-crown-6 (18C6) or its derivatives can be used, which, however, have not been widely studied for these purposes. In our work, the key property of 18C6 and its derivatives, the phase distribution, was studied using tritium labeling. The possibility of introducing a tritium label into CEs molecules using thermal activation of tritium has been demonstrated; a high specific activity of the obtained compounds was achieved (from 18 to 108 TBq/mol). Methods for chromatographic purification of the studied CEs were developed. The distribution of 18C6 and its derivatives between various organic solvents and water was studied in detail for the first time. Subsequently, the obtained data will allow us to choose conditions for the selective recovery of 226Ra from aged sources

Recovery of 177Lu from Irradiated HfO2 Targets for Nuclear Medicine Purposes

A new method of production of one of the most widely used isotopes in nuclear medicine, 177Lu, with high chemical purity was developed; this method includes irradiation of the HfO2 target with bremsstrahlung photons. The irradiated target was dissolved in HF and then diluted and placed onto a column filled with LN resin. Quantitative sorption of 177Lu could be observed during this process. The column later was rinsed with the mixture of 0.1 M HF and 1 M HNO3 and then 2 M HNO3 to remove impurities. Quantitative desorption of 177Lu was achieved by using 6 M HNO3. The developed method of 177Lu production ensures high purification of this isotope from macroquantities of hafnium and zirconium and radioactive impurities of carrier-free yttrium. The content of 177mLu in 177Lu in photonuclear production was determined. Due to high chemical and radionuclide purity, 177Lu obtained by the developed method can be used in nuclear medicine

Yields of Photo-Proton Reactions on Nuclei of Nickel and Separation of Cobalt Isotopes from Irradiated Targets

Nowadays, cobalt isotopes 55Co, 57Co, and 58mCo are considered to be promising radionuclides in nuclear medicine, with 55Co receiving the most attention as an isotope for diagnostics by positron emission tomography. One of the current research directions is dedicated to its production using electron accelerators (via photonuclear method). In our work, the yields of nuclear reactions occurring during the irradiation of natNi and 60Ni by bremsstrahlung photons with energy up to 55 MeV were determined. A method of fast and simple cobalt isotopes separation from irradiated targets using extraction chromatography was developed

Photonuclear Alchemy: Obtaining Medical Isotopes of Gold from Mercury Irradiated on Electron Accelerators

In our work, the photonuclear production of 198,199Au isotopes for nuclear medicine purposes was studied, and a method for their recovery from irradiated mercury was developed. The yields of the corresponding nuclear reactions were determined, and a comparison of various methods of obtaining gold radioisotopes was provided. New sorbents based on benzo-15-crown-5, which selectively binds gold, were studied, and the optimal conditions for Au recovery with a high degree of purification from mercury were found. It was established that, for the fast and quantitative recovery of Au isotopes, it was necessary to add at least 0.1 mg of the carrier. As a result, the developed method can be regularly used to obtain 198,199Au for the research of radiopharmaceuticals based on them

Structure–Activity Relationships and Transcriptomic Analysis of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors

To evaluate the differences in action of commercially available 2-oxoglutarate mimetics and “branched-tail” oxyquinoline inhibitors of hypoxia-inducible factor prolyl hydroxylase (HIF PHD), the inhibitors’ IC50 values in the activation of HIF1 ODD-luciferase reporter were selected for comparative transcriptomics. Structure–activity relationship and computer modeling for the oxyquinoline series of inhibitors led to the identification of novel inhibitors, which were an order of magnitude more active in the reporter assay than roxadustat and vadadustat. Unexpectedly, 2-methyl-substitution in the oxyquinoline core of the best HIF PHD inhibitor was found to be active in the reporter assay and almost equally effective in the pretreatment paradigm of the oxygen-glucose deprivation in vitro model. Comparative transcriptomic analysis of the signaling pathways induced by HIF PHD inhibitors showed high potency of the two novel oxyquinoline inhibitors (#4896-3249 and #5704-0720) at 2 μM concentrations matching the effect of 30 μM roxadustat and 500 μM dimethyl oxalyl glycine in inducing HIF1 and HIF2-linked pathways. The two oxyquinoline inhibitors exerted the same activation of HIF-triggered glycolytic pathways but opposite effects on signaling pathways linked to alternative substrates of HIF PHD 1 and 3, such as p53, NF-κB, and ATF4. This finding can be interpreted as the specificity of the 2-methyl-substitute variant for HIF PHD2

Bioactive Flavonoids and Catechols as Hif1 and Nrf2 Protein Stabilizers - Implications for Parkinson’s Disease

Flavonoids are known to trigger the intrinsic genetic adaptive programs to hypoxic or oxidative stress via estrogen receptor engagement or upstream kinase activation. To reveal specific structural requirements for direct stabilization of the transcription factors responsible for triggering the antihypoxic and antioxidant programs, we studied flavones, isoflavones and catechols including dihydroxybenzoate, didox, levodopa, and nordihydroguaiaretic acid (NDGA), using novel luciferase-based reporters specific for the first step in HIF1 or Nrf2 protein stabilization. Distinct structural requirements for either transcription factor stabilization have been found: as expected, these requirements for activation of HIF ODD-luc reporter correlate with in silico binding to HIF prolyl hydroxylase. By contrast, stabilization of Nrf2 requires the presence of 3,4-dihydroxy- (catechol) groups. Thus, only some but not all flavonoids are direct activators of the hypoxic and antioxidant genetic programs. NDGA from the Creosote bush resembles the best flavonoids in their ability to directly stabilize HIF1 and Nrf2 and is superior with respect to LOX inhibition thus favoring this compound over others. Given much higher bioavailability and stability of NDGA than any flavonoid, NDGA has been tested in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-animal model of Parkinson’s Disease and demonstrated neuroprotective effects