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Mastren, Tara

Publications and source records attributed to Mastren, Tara.

10 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

The production and separation of 161 Tb with high specific activity at the University of Utah

Targeted radiotherapy (TRT) is an increasingly prominent area of research in nuclear medicine, particularly in the context of treating cancerous tumors. One radionuclide of considerable interest for TRT is terbium-161 (t 1/2 = 6.95 days), which undergoes beta emission and shares similar decay properties as 177 Lu (FDA-approved as LUTATHERA® and PLUVICTO®). Besides beta emission, 161 Tb also emits a significant number of conversion and Auger electrons further enhancing its therapeutic potential. Terbium-161 can be produced using nuclear reactors through an indirect neutron capture reaction, $^{160}_{64}$Gd(n,γ) $^{161}_{64}$Gd → (3.7 min, β – ) $^{161}_{65}$Tb, from 160 Gd targets. However, a key challenge in utilizing 161 Tb for TRT lies in effectively separating target and product materials to attain high specific activity for radiolabeling. Here, we detail the production of no-carrier added 161 Tb using low flux research reactors (mean thermal (< 0.625 eV) neutron flux: 1.356 ×10 12 n • cm –2 • s –1 ) like the University of Utah TRIGA Reactor, using enriched 160 Gd 2 O 3 targets (1.5 ± 0.3 µCi of 161 Tb per mg of 160 Gd target per hour of irradiation). We also developed a separation technique based on cation exchange and extraction chromatography, suitable for mCi level irradiations with targets exceeding 200 milligrams. In a simulated full-scale irradiation, 161 Tb was successfully isolated from large mass targets using cation exchange (AG 50W-X8, with 2-hydroxyisobutyric acid at 70 mM, pH 4.75) and extraction chromatography (LN Resin, 0.5 – 0.75 M HNO 3 ) methods. Here, this resulted in high apparent molar activities of [ 161 Tb]Tb-DOTA (113 ± 3 MBq/nmol), demonstrating high purity 161 Tb relevant for potential future preclinical applications.

161Tb↗
DOE OSTI2024

Adsorption of terbium (III) on DGA and LN resins: Thermodynamics, isotherms, and kinetics

Two commercially available extraction chromatography (EXC) resins containing N,N,N’,N’-tetra-n-octyldiglycolamide (DGA Resin, Normal, 50 – 100 μm) and Bis(2-ethylhexyl) phosphate (LN Resin, 100 – 150 μm) were used as adsorbents to study fundamental adsorption properties such as thermodynamic values, equilibrium isotherms, and kinetic uptake models for terbium(III) adsorption. Weight distribution ratios (D w ) for terbium on DGA and LN resins were measured using a [ 160 Tb]Tb 3+ radiometric tracer in nitric acid as a function of acidity, temperature, initial analyte concentration, and equilibrium time. The D w values showed increasing binding affinity for DGA resin at high nitric acid concentrations and decreasing binding affinity for LN resins. Thermodynamic studies for DGA and LN resins revealed that the Gibbs free energy (ΔG) increased consistently with temperature. To model equilibrium data, increasingly higher parameter equilibrium isotherm models (Henry (1) < Langmuir, Freundlich (2) < Redlich-Peterson (3) < Fritz-Schluender (4)) were compared on their root mean squared errors (RMSE) and adjusted determination coefficients to determine the most applicable model. In all cases, the empirical four-parameter Fritz-Schluender isotherm demonstrated a superior fit. Similar comparisons for reaction-based kinetic models (Pseudo-first-order < Pseudo-second-order < Pseudo-n-order) revealed that the higher-order PNO model yielded a superior fit of kinetic data for both resins. Furthermore, in some cases, adsorption isotherms and kinetic models could also be modeled by a lower-order model with minimal change in error parameters. Weber-Morris plots revealed that two linear sections are observed for each resin, where the first linear segment is attributed to fast (film diffusion) adsorption of terbium, followed by slower intraparticle diffusion of terbium through the pores as the rate-limiting step. Based on the Weber-Morris plot, both film and intraparticle diffusion are involved in controlling the kinetic rate of adsorption for DGA and LN resins.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2024

An electrochemical generator for the continual supply of 213 Bi from 225 Ac for use in targeted alpha therapy applications

Bismuth-213 is a radionuclide of interest for targeted alpha therapy and is supplied via a radiochemical generator system through the decay of 225 Ac. Radionuclide generators employ longer lived “parent” radionuclides to routinely supply shorter-lived “daughter” radionuclides. The traditional 225 Ac/ 213 Bi radiochemical generator relies on an organic cation exchange resin where 225 Ac binds to the resin and 213 Bi is routinely eluted. These resins degrade when they absorb large doses of ionizing radiation (>1 × 10 6 Gy/mg), which has been observed when the loading activity of 225 Ac exceeds 2.59*10 9 Bq (70 mCi). Herein we report the development of an electrochemical generator for the supply of 213Bi that has the potential to overcome this limitation. Bismuth-213 spontaneously electrodeposits onto nickel foils in 0.1 M hydrochloric acid at 70 °C. Using this method, we were able to plate an average of 73 ± 4 % of the 213 Bi in solution and obtain a final 213 Bi recovery of 65 ± 8 % in 0.1 M citrate pH 4.5 via reverse electrolysis using titanium as the cathode. The recovered 213Bi had an average radiochemical purity of >99.8 % and was successfully used to radiolabel DOTATATE with an average radiochemical yield of 85.1 % (not optimized).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Investigating sol–gel matrix loading capacity toward producing surrogate nuclear explosive debris with realistic composition

Post detonation nuclear forensic materials which resemble the size, color, elemental composition, and radionuclide content of real nuclear debris would be valuable for developing and validating new nuclear forensic techniques. As nuclear fallout types vary significantly, the ability to tailor each of these parameters accurately is desired to produce materials capable of testing analytical methods under a wide array of forensic scenarios. Sol–gel synthesis techniques can provide tunability of size, shape and composition for producing a wide variety of solid nuclear forensics benchmarking materials. Further, the sol–gel process consists of forming a metal oxide material, often silica, through polymerization of a metal-alkoxy precursor. In this work, we characterize the ability to load sol–gel particles with secondary elemental components such as iron, aluminum, and calcium toward producing benchmarking materials approximating the elemental composition of historic nuclear debris from the Nevada National Security Site. We also demonstrate quantitative radionuclide encapsulation toward producing benchmarking materials with controllable radionuclide content. Finally, we employ these techniques to produce nuclear debris benchmarking materials with controllable elemental matrix composition and radionuclide content and compare these samples with the composition of a historic fallout sample previously reported from the Nevada National Security Site.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Design and synthesis of astatinated benzothiazole compounds for their potential use in Targeted Alpha Therapy (TAT) strategies to treat Alzheimer's disease-associated amyloid plaques

Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by the buildup of amyloid fibrils, amorphous aggregates and tauopathies. Several treatment modalities, which rely on various biological processes to reduce disease burden, have been largely ineffective at treating Alzheimer's disease. Targeted alpha therapy (TAT) has demonstrated positive results in the treatment of cancer. Benzothiazole derivatives have been successfully shown to target these plaques and are used in several imaging applications. One such derivative, Flutemetamol (Vizamyl TM ) is an FDA approved diagnostic tool for PET imaging of AD-associated plaques. We report the radiolabeling of benzothiazole derivatives with 211 At, a 7.2 h alpha emitting radionuclide, using a copper catalyzed reaction with a boronic acid precursor molecule. In conclusion, our final compound [ 211 At]3'-At-PIB-OMe had a radiochemical yield of 55% and was found to be stable for at least 3 h in phosphate buffered saline.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

Development of Anti- Yersinia pestis Human Antibodies with Features Required for Diagnostic and Therapeutic Applications

Yersinia pestis is a category A infective agent that causes bubonic, septicemic, and pneumonic plague. Notably, the acquisition of antimicrobial or multidrug resistance through natural or purposed means qualifies Y. pestis as a potential biothreat agent. Therefore, high-quality antibodies designed for accurate and sensitive Y. pestis diagnostics, and therapeutics potentiating or replacing traditional antibiotics are of utmost need for national security and public health preparedness. Here, we describe a set of human monoclonal immunoglobulins (IgG1s) targeting Y. pestis fraction 1 (F1) antigen, previously derived from in vitro evolution of a phage-display library of single-chain antibodies (scFv). We extensively characterized these antibodies and their effect on bacterial and mammalian cells via: ELISA, flow cytometry, mass spectrometry, spectroscopy, and various metabolic assays. Two of our anti-F1 IgG (αF1Ig 2 and αF1Ig 8) stood out for high production yield, specificity, and stability. These two antibodies were additionally attractive in that they displayed picomolar affinity, did not compete when binding Y. pestis, and retained immunoreactivity upon chemical derivatization. Most importantly, these antibodies detected < 1,000 Y. pestis cells in sandwich ELISA, did not harm respiratory epithelial cells, induced Y. pestis agglutination at low concentration (350 nM), and caused apparent reduction in cell growth when radiolabeled at a nonagglutinating concentration (34 nM). These antibodies are amenable to the development of accurate and sensitive diagnostics and immuno/radioimmunotherapeutics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

A reverse 230 U/ 226 Th radionuclide generator for targeted alpha therapy applications

Thorium-226 (half-life 30.6 m) is a radionuclide of interest for use in targeted alpha therapy applications. Additionally, due to its short half-life, 226 Th must be provided through a radionuclide generator system from its parent 230 U (20.8 d). Furthermore, as the half-life of 226 Th is very short, it should be provided in a form that is directly amenable to use in biomedical applications.

226-Th↗
DOE OSTI2020

Thorium chelators for targeted alpha therapy: Rapid chelation of thorium-226

We report one of the main challenges in targeted alpha therapy is assuring delivery of the α-particle dose to the targeted cells. Thus, it is critical to identify ligands for α-emitting radiometals that will form complexes that are very stable, both in vitro and in vivo. In this investigation, thorium-227 (t 1/2 = 18.70 days) chelation of ligands containing hydroxypyridinonate (HOPO) or picolinic acid (pa) moieties and the stability of the resultant complexes were studied. Chelation reactions were followed by reversed-phased HPLC and gamma spectroscopy. Studies revealed that high 227 Th chelation yields could be obtained within 2.5 h or less with ligands containing four Me-3,2-HOPO moieties, 1 (83%) and 2 (65%), and also with ligands containing pa moieties, H 4 octapa 3 (65%) and H 4 py4pa 6 (87%). No reaction occurred with H 4 neunpa-p-Bn-NO 2 4, and the chelation reaction with another pa ligand H 4 pypa 5 gave inconsistent yields with a very broad radio-HPLC peak. The ligands spermine-(Me-3,2-HOPO) 4 1, H 4 octapa 3, and H 4 py4pa 6 had high stability (i.e., 87% of 227 Th still bound to the ligand) in phosphate-buffered saline at room temperature over a 6-day period. Preliminary studies with ligand 6 demonstrated efficient chelation of thorium-226 (t 1/2 = 30.57 min) when heated to 80°C for 5 min.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Extraction chromatography of 225 Ac and lanthanides on N,N-dioctyldiglycolamic acid /1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide solvent impregnated resin

The alpha-emitter 225 Ac (t 1/2 = 9.92 d) is currently under development for targeted alpha-particle therapy of cancer, and accelerator production of 225 Ac via proton irradiation of thorium targets requires robust separations of 225 Ac from chemically similar fission product lanthanides. Additionally, the lanthanide elements represent critical components in modern technologies, and radiolanthanides such as 140 Nd (t 1/2 = 3.37 d) also have potential application in the field of nuclear medicine. The ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Bmim][NTf 2 ]), combined with the diglycolamide extractant, N,N-dioctyldiglycolamic acid (DODGAA), was adsorbed on macroporous resin support to produce a solvent impregnated resin (SIR) that was investigated for separations of 225 Ac and lanthanides. The equilibrium distribution coefficients (Kd) of the rare earth elements (Sc(III), Y(III), Ln(III)), 225 Ac(III), Th(IV), and U(VI) on the prepared DODGAA/[Bmim][NTf 2 ]-SIR were determined from batch adsorption experiments in HCl and HNO 3 media. The DODGAA/[Bmim][NTf2]-SIR exhibited preferential uptake of the heavier lanthanide elements while allowing for the separation of the lighter lanthanides. Column separations utilizing the DODGAA/[Bmim][NTf 2 ]-SIR were effective at separating the lighter lanthanides from each other, and separating 225 Ac from a mixture of lanthanides, 213 Bi, and 225 Ra without the need for additional complexing agents.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗