Efficient late-stage formation of aryl-211At bonds is relevant to expanding the scope of targeted α-therapy radiopharmaceuticals. In this work, a catalyst-enabled astatodeboronation approach is evaluated using wet chemically regenerated 211At recovered from shipped 3-octanone-impregnated columns. A series of aryl boronic esters bearing electron-donating and electron-withdrawing substituents were radiolabeled under mild conditions, with reaction parameters examined through time-dependent studies. Radiochemical conversions ranging from 68-97% were observed across the substrate set. Density functional theory calculations were employed as a qualitative framework to contextualize relative B-C and At-C bonding descriptors. Overall, this study demonstrates that wet chemically regenerated 211At can be applied to the late-stage labeling of aryl boronic esters under mild conditions and provides guidance for future exploration of 211At radiolabeling strategies.

The ion exchange behavior of K‐ and Cs‐derivatives of α‐zirconium phosphate, A‐ZrP, with the targeted alpha therapy (TAT) radionuclide 211At, as At+ and AtO+, has been investigated. The K‐ZrP shows strong affinity for both At+ and AtO+, ≥99% uptake. The affinity to Cs‐ZrP was less pronounced, 87%–94% uptake, favoring At+. The binding strength was tested against several leaching solutions, including carbonate, phosphate buffered saline (PBS), 4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid (HEPES) buffers, and ethylenediaminetetraacetic acid (EDTA) solutions at various concentrations (0.1–10 mM). K‐ZrP retained 211At in all buffer and EDTA solutions up to 1 mM (<0.5% leaching). The Cs‐ZrP showed no leaching of At+, while AtO+ leached (1%–3%) in the carbonate and HEPES buffers, along with all of the EDTA solutions, with complete retention only in the PBS buffer. In all cases, when the EDTA concentration reached 10 mM, 211At leaching was observed. Once incorporated into the ZrP nanoplatelets, significant shielding of the α‐particles was observed, not only attenuating the intensity of the emission but also reducing the energy of the α‐particles themselves exiting the nanoplatelets. These properties provide the basis for K‐ZrP, and to a lesser extent, Cs‐ZrP to be further considered as potentially promising candidates for a delivery mechanism of 211At for application in TAT.

The formation of a stable alkyl At-C bond occurs during the shipment of 211At on a 3-octanone-impregnated column and the reactivity of 211At stripped from columns has been studied. The 211At could not be recovered from the 3-octanone organic phase using nitric acid or sodium hydroxide, even up to 10 and 15.7 M, respectively. Several reducing and oxidizing agents, including hydrazine, hydroxylamine, ascorbic acid, ceric ammonium nitrate, potassium permanganate, sodium hypochlorite, and calcium hypochlorite were used to promote the recovery of 211At. The most effective reducing agent was hydroxylamine, where ∼70% of the 211At was recovered, while among oxidizing agents ceric ammonium nitrate, potassium permanganate, and sodium hypochlorite all showed near quantitative recovery of 211At. These results indicate an At-C bond is being formed during the shipment of the column and a redox reaction is required for bond cleavage to occur. DFT calculations have been used to propose several products of an AtO+-3-octanone reaction, with 4-astato-5-hydroxy-octa-3-one being the most probable.

Cyclotron Institute at Texas A&M University started a project to develop the reacceleration of radioactive ions using the two operational cyclotrons and a Charge Breeding ECR ion source. The radioactive ions are produced primarily via (p,n) reactions using the IGISOL technique. The reaction products are transported into a Charge Breeder ECR ion source where their charge state is boosted from 1+ to higher charge states. The transport of the radioactive products and the injection into the ion source are very important for the efficiency of charge breeding. Two techniques have been used: acceleration-deceleration method (classic) and low - energy RF-only sextupole ion guide transport and injection method (innovative technique). The last method appears to be very efficient and great charge breeding efficiency was observed. The presentation of the entire project, the new injection technique, experimental results, and future plans will be discussed.

A new 3He-driven IGISOL production station and mass separator have been designed to produce neutron-deficient low-mass isotopes at the Cyclotron Institute for the TAMUTRAP facility. The LSTAR design has a mass resolution M/ΔM≥3,000 to reject contaminants with >95% efficiency.

The alpha emitter astatine-211 (211At) is a promising candidate for cancer treatment based on Targeted Alpha (α) Therapy (TAT). A small number of facilities, distributed across the United States, are capable of accelerating α-particle beams to produce 211At. However, challenges remain regarding strategic methods for shipping 211At in a form adaptable to advanced radiochemistry reactions and other uses of the radioisotope. PURPOSE:Our method allows shipment of 211At in various quantities in a form convenient for further radiochemistry. PROCEDURES:For this study, a 3-octanone impregnated Amberchrom CG300M resin bed in a column cartridge was used to separate 211At from the bismuth matrix on site at the production accelerator (Texas A&M) in preparation for shipping. Aliquots of 6 M HNO3 containing up to ≈2.22 GBq of 211At from the dissolved target were successfully loaded and retained on columns. Exempt packages (<370 MBq) were shipped to a destination radiochemistry facility, University of Texas MD Anderson Cancer Center, in the form of a convenient air-dried column. Type A packages have been shipped overnight to University of Alabama at Birmingham. MAIN FINDINGS:Air-dried column hold times of various lengths did not inhibit simple and efficient recovery of 211At. Solution eluted from the column was sufficiently high in specific activity to successfully radiolabel a model compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1), with 211At. The method to prepare and ship 211At described in this manuscript has also been used to ship larger quantities of 211At a greater distance to University of Alabama at Birmingham. PRINCIPAL CONCLUSIONS:The successful proof of this method paves the way for the distribution of 211At from Texas A&M University to research institutions and clinical oncology centers in Texas and elsewhere. Use of this simple method at other facilities has the potential increase the overall availability of 211At for preclinical and clinical studies.

Astatine sorption by ion exchange resins from nitric acid media.

The Texas A&M University Cyclotron Institute Radiation Effects Facility has made several facility developments in the preceding years including the addition of 9.4 and 15 MeV/u heavy ion beams to the K150 SEELine, a new heavy ion beam to the K500 SEELine, a second ECR ion source for the K500 SEELine, and a remote DUT heating system to both SEELines. The additions of heavy ion beam testing to the K150 SEELine and the second ECR ion source to the K500 in particular have improved reliability and uptime of beam hours provided by the Cyclotron Institute to address the growing demand for beam time in the radiation effects testing industry.

The reaction of a 100Mo beam at 12 MeV/nucleon impinging on a 4He gas-cell target was performed. The 99Mo alongside other coproduced isotopes were collected after the gas target on an aluminum catcher foil and their respective radioactivities were measured by offline γ-ray analysis. In this contribution, preliminary experimental results which are used to discuss the possibility of optimal large-scale production conditions of the produced radioisotopes are presented.

Astatine is one of the least chemically studied elements and its behavior in the presence of non-conventional solvents has not been investigated before. This work considers both hydrophobic ionic liquids and binary mixtures as alternatives to conventional solvents. The study is based on the extraction of astatine and bismuth (target material required to produce astatine) into imidazolium-based ionic liquid, and binary mixtures formed by active pharmaceuticals (ibuprofen, lidocaine) and a food-grade ingredient (methyl anthranilate). It is shown that both the ionic liquid and binary mixtures can successfully extract At from nitric acid media, but extraction of Bi into the ionic liquid is very inefficient, resulting in a good separation factor for these two elements in the entire studied acidity range. Extraction of At into binary mixtures is very efficient, having distribution ratio values as high as 1000, while the behavior of Bi under these conditions depends on the composition of the mixture. A mathematical model has been developed to fit both At and Bi experimental data and applied to determine corresponding thermodynamic extraction constants.

Systematic study of astatine (At) sorption on extraction chromatography resins from nitric acid media has been performed at Texas A&M University. This work covers commercially available resins such as LN, TK400, SR, TRU, and UTEVA. Acquiring an understanding of At behavior in up to 4 M HNO3 solutions is a key step to develop a rapid and reliable system for At separation and purification. The determined distribution coefficients are greater than 20 for all the resins studied, reaching 400 for TRU and UTEVA resins. The sorption uptake decreases in the order: TRU greater than or similar to UTEVA > TK400 greater than or similar to SR > LN. For each resin a thermodynamic model has been developed to suggest a possible mechanism of At sorption and corresponding sorption constants have been estimated. Literature data along with new results on bismuth (Bi) sorption by studied resins in nitric acid media have been reviewed and a mathematical model to describe its behavior has been suggested. A ratio of corresponding fit functions of At and Bi assigned to the same resin and acidity has been used to estimate separation factors of these elements. Only the TRU resin is not suitable for efficient At isolation from Bi, while the other four resins demonstrate promising results.

A detailed study of At and Bi extraction from nitric acid media into conventional solvents, namely 1-octanol and methyl anthranilate, has been performed. The analysis includes a mathematical modeling which allows the fitting of experimental data and determination of extraction constants of the two above mentioned elements. Also, this approach helped to estimate a stability constant of a weak AtO(NO3) complex along with thermodynamic constants describing the redox process of At species in the acidic solution and formation of an adduct of Bi in the presence of methyl anthranilate. The results of the fitting have been used to calculate corresponding separation factors of Bi and At as well. Moreover, a computational study has been performed to evaluate At interaction with the above mentioned solvents.

Ketones have been proven effective in extracting astatine(III) from aqueous solvents. Previous theoretical studies suggested a mechanism where the "sp2" lone pair on the carbonyl oxygen donates electron density into the π system of the AtO+ molecular cation to form a dative-type bond. In this study, co-extraction of NO3- as AtO(NO3)·(O═CR1R2) species into the organic phase appears to be a key factor. Adjusting the electronic properties of the ketone, by having an aryl group instead of an alkyl group in the alpha position of the ketone, increased the electron density on C═O, increased the bond strength between the ketone and AtO+, and in turn increased the extraction of 211At into the organic phase. Extraction with diketones shows dependence on the bridging distance between the two carbonyl moieties, where a C3 or longer bridge results in a 10-fold increase in extraction into the organic phase. DFT calculations show the longer bridge allows for the chelation of AtO(NO3) by either the second carbonyl or the phenyl ring.

Automation of irradiated bismuth target dissolution and astatine recovery from nitric acid media has been achieved at Texas A&M University. This process can be controlled remotely; it does not require any chemical treatment or evaporation of dissolution solution prior to the separation of above-mentioned elements on an extraction chromatography column, making the final product ready within 20 min. The accompanying radioimpurities have been identified and successfully separated from astatine, leading to greater than 99% radiopurity of the desired fractions. The system consists of only one pump and a set of LabVIEW controlled valves, and allows the connection of up to 10 different columns, providing the opportunity to prepare a variety of air dry columns, which can be different column geometries, containing astatine ready for further chemistry or shipment to desired facilities.

The Texas A&M University Penning Trap (TAMUTRAP) facility aims to test the standard model of the electroweak interaction by measuring the beta-v correlation parameter, alpha(beta v), for beta-delayed proton emitters in the atomic mass range 20 < A < 40. Precision measurements of this correlation parameter and, inextricably, the Fierz interference parameter, are a sensitive probe of physics beyond the standard model. Using off-line ion sources, the TAMUTRAP facility has been commissioned by demonstrating the ability to manipulate the trapped-ion motions as well as to perform precision mass measurements. Our novel cylindrical Penning trap - the world's largest - differs from typical designs in two key aspects: the electrode structure has an 180-mm inner diameter and an overall length of 334.89 mm leading to a uniquely small length/radius ratio l/r = 3.72; and we do not use the long end cap approximation, instead our short endcap electrodes are closed and capable of being placed at an arbitrary potential. This geometry is optimized for observing beta-delayed proton decays, but is also well suited for other in-trap and post-trap precision decay experiments. In addition to presenting an overview of the TAMUTRAP facility, we demonstrate that our unique Penning trap is able to measure masses with a precision similar to typical trap designs. (C) 2021 Elsevier B.V. All rights reserved.

The near quantitative separation, purification, and recovery of At-211 has been demonstrated through an extraction chromatography process which utilizes porous beads impregnated with 3-octanone, resulting in an elution yield of 92-95%. Moreover, the rapid nature of this process, <20 min, was achieved after dissolution of a Bi metal target in HNO3 following retrieval from the beamline after alpha-particle bombardment. The solution was directly loaded onto the column with no volume or acidity adjustment. The column was washed with HNO3 and H2O, and At-211 was eluted with ethanol, collecting roughly 87-93% in 1 mL. This process of recovering high purity At-211, in near quantitative yields, represents a significant advance in At separations.

Alpha emitting radionuclides with medically relevant half-lives are interesting for treatment of tumors and other diseases because they deposit large amounts of energy close to the location of the radioisotope. Researchers at the Cyclotron Institute at Texas A&M University are developing a program to produce 211At, an alpha emitter with a medically relevant half-life. The properties of 211At make it a great candidate for targeted alpha therapy for cancer due to its short half-life (7.2 h). Astatine-211 has now been produced multiple times and reliability of this process is being improved.

The inverse kinematics methodology using a gas target has been applied to produce medically important radionuclides at the Cyclotron Institute at Texas A&M University. The production of the theranostic radionuclide 67 Cu (T1/2 = 62 h) through the reaction of a 70 Zn beam at 15 MeV/nucleon with a hydrogen gas target was performed. The activities at end of irradiation and the thick target yield were obtained for 67 Cu. A test using the forward-focused neutrons from the primary reaction to irradiate nat Zn to produce 67 Cu is also presented.