Search Results (9)

With low background radiation, tritiate compounds exclusively emit intense beta particles without structural changes. This makes them a useful tool in the drug discovery arsenal. Thanks to the recent rapid progress in tritium chemistry, the preparation and analysis of tritium-labeled compounds are now much easier, simpler, and cheaper. Pharmacokinetics, autoradiography, and protein binding studies have been much more efficient with the employment of tritium-labeled compounds. This review provides a comprehensive overview of tritium-labeled compounds regarding their properties, synthesis strategies, and applications. Full article

Bovine serum albumin (BSA) was ³H-labeled via a tritium thermal activation method that allowed quantifying BSA adsorption on single-walled carbon nanotubes (SWCNTs) to be 740 mg/mg, which leads to the ζ-potential of the BSA–SWCNT complex changing from −10 to −16 mV. Supercomputer simulations were carried out with Gromacs and PM7 with MOPAC2016 with Berendsen, Nosè–Hoover and Parrinello–Rahman algorithms. The dominant interactions between BSA and SWCNTs are found to be hydrophobic, and hydrogen bonds are also present. The mean total energy of the Coulomb and Van der Waals interactions is −646 ± 8 kJ/mol, by gmx energy. Full article

Coatings with xenogenic materials, made of detonation nanodiamonds, provide additional strength and increase elasticity. A functionally developed surface of nanodiamonds makes it possible to apply antibiotics. Previous experiments show the stability of such coatings; however, studies on stability in the bloodstream and calcification of the material in natural conditions have yet to be conducted. Tritium-labeled nanodiamonds (negative and positive) were obtained by the tritium activation method and used to develop coatings for a pork aorta to analyze their stability in a pig’s bloodstream using a radiotracer technique. A chitosan layer was applied from a solution of carbonic acid under high-pressure conditions to prevent calcification. The obtained materials were used to prepare a porcine conduit, which was surgically stitched inside the pig’s aorta for four months. The aorta samples, including nanodiamond-coated and control samples, were analyzed for nanodiamond content and calcium, using the radiotracer and ICP-AES methods. A histological analysis of the materials was also performed. The obtained coatings illustrate a high in vivo stability and low levels of calcification for all types of nanodiamonds. Even though we did not use additional antibiotics in this case, the development of infection was not observed for negatively charged nanodiamonds, opening up prospects for their use in developing coatings. Full article

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. Full article

This research is focused on the adsorption modification of detonation nanodiamond surfaces with antibiotics for their further use as smart materials for cardiovascular surgery purposes, namely as bioprostheses modifiers. Tritium-labeled amikacin and levofloxacin were used as tracers for the adsorption process control. We found that nanodiamonds form adsorption complexes with levofloxacin via physical adsorption, while in the case of amikacin, electrostatic attraction contributes to the formation of more stable complexes, even in the presence of electrolytes and desorbing agents (models of biological fluids). Antimicrobial characterization of nanodiamond–levofloxacin and nanodiamond–amikacin complexes indicates a reduction in the dose of antibiotics that is used as an antimicrobial agent. Therefore, the use of biomaterial based on DND complexes with antibiotics as the basis of bioprostheses will allow one either to avoid or significantly reduce the duration and intensity of antibiotics use in the postoperative period, which is critically important from the viewpoint of the development of antibiotic resistance in pathogens. Full article

Natural products (e.g., polyphenols) have been used as biologically active compounds for centuries. Still, the mechanisms of biological activity of these multicomponent systems are poorly understood due to a lack of appropriate experimental techniques. The method of tritium thermal bombardment allows for non-selective labeling and tracking of all components of complex natural systems. In this study, we applied it to label two well-characterized polyphenolic compounds, peat fulvic acid (FA-Vi18) and oxidized lignin derivative (BP-Cx-1), of predominantly hydrophilic and hydrophobic character, respectively. The identity of the labeled samples was confirmed using size exclusion chromatography. Using ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT ICR MS), key differences in the molecular composition of BP-Cx-1 and FA-Vi18 were revealed. The labeled samples ([³H]-FA-Vi18 (10 mg/kg) and [³H]-BP-Cx-1 (100 mg/kg)) were administered to female BALB/c mice intravenously (i.v.) and orally. The label distribution was assessed in blood, liver, kidneys, brain, spleen, thymus, ovaries, and heart using liquid scintillation counting. Tritium label was found in all organs studied at different concentrations. For the fulvic acid sample, the largest accumulation was observed in the kidney (C_max 28.5 mg/kg and 5.6 mg/kg, respectively) for both routes. The organs of preferential accumulation of the lignin derivative were the liver (C_max accounted for 396.7 and 16.13 mg/kg for i.v. and p.o. routes, respectively) and kidney (C_max accounted for 343.3 and 17.73 mg/kg for i.v. and p.o. routes, respectively). Our results demonstrate that using the tritium labeling technique enabled successful pharmacokinetic studies on polyphenolic drugs with very different molecular compositions. It proved to be efficient for tissue distribution studies. It was also shown that the dosage of the polyphenolic drug might be lower than 10 mg/kg due to the sensitivity of the ³H detection technique. Full article

Poly (ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme in the DNA repair process and the target of several FDA-approved inhibitors. Several of these inhibitors have been radiolabeled for non-invasive imaging of PARP-1 expression or targeted radiotherapy of PARP-1 expressing tumors. In particular, derivatives of olaparib and rucaparib, which have reduced trapping potency by PARP-1 compared to talazoparib, have been radiolabeled for these purposes. Here, we report the first radiosynthesis of [¹⁸F]talazoparib and its in vitro and in vivo evaluation. Talazoparib (3a″) and its bromo- or iodo-derivatives were synthesized as racemic mixtures (3a, 3b and 3c), and these compounds exhibit high affinity to PARP-1 (K_i for talazoparib (3a″): 0.65 ± 0.07 nM; 3a: 2.37 ± 0.56 nM; 3b: 1.92 ± 0.41 nM; 3c: 1.73 ± 0.43 nM; known PARP-1 inhibitor Olaparib: 1.87 ± 0.10 nM; non-PARP-1 compound Raclopride: >20,000 nM) in a competitive binding assay using a tritium-labeled PARP-1 radioligand [³H]WC-DZ for screening. [¹⁸F]Talazoparib (3a″) was radiosynthesized via a multiple-step procedure with good radiochemical and chiral purities (98%) and high molar activity (28 GBq/μmol). The preliminary biodistribution studies in the murine PC-3 tumor model showed that [¹⁸F]talazoparib had a good level of tumor uptake that persisted for over 8 h (3.78 ± 0.55 %ID/gram at 4 h and 4.52 ± 0.32 %ID/gram at 8 h). These studies show the potential for the bromo- and iodo- derivatives for PARP-1 targeted radiotherapy studies using therapeutic radionuclides. Full article

The phytohormone abscisic acid (ABA) plays an important role in plant growth and in response to abiotic stress factors. At the same time, its accumulation in soil can negatively affect seed germination, inhibit root growth and increase plant sensitivity to pathogens. ABA is an inert compound resistant to spontaneous hydrolysis and its biological transformation is scarcely understood. Recently, the strain Rhodococcus sp. P1Y was described as a rhizosphere bacterium assimilating ABA as a sole carbon source in batch culture and affecting ABA concentrations in plant roots. In this work, the intermediate product of ABA decomposition by this bacterium was isolated and purified by preparative HPLC techniques. Proof that this compound belongs to ABA derivatives was carried out by measuring the molar radioactivity of the conversion products of this phytohormone labeled with tritium. The chemical structure of this compound was determined by instrumental techniques including high-resolution mass spectrometry, NMR spectrometry, FTIR and UV spectroscopies. As a result, the metabolite was identified as (4RS)-4-hydroxy-3,5,5-trimethyl-4-[(E)-3-oxobut-1-enyl]cyclohex-2-en-1-one (dehydrovomifoliol). Based on the data obtained, it was concluded that the pathway of bacterial degradation and assimilation of ABA begins with a gradual shortening of the acyl part of the molecule. Full article

Nanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adults due in the vast majority to the EWS-FLI1 junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against EWS-FLI1 inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA. Full article