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The promise of 225 Ac targeted alpha therapies has been on the horizon for the last two decades. TerraPower Isotopes are uniquely suited to produce clinically relevant quantities of 225 Ac through the decay of 229 Th. Herein, a rapid processing scheme to isolate radionuclidic and radioisotopically pure 225 Ac in good yield (98%) produced from 229 Th that contains significant quantities of 228 Th activity is described. The characterization of each step of the process is presented along with the detailed characterization of the resulting 225 Ac isotopic starting material that will support the cancer research and development efforts., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Increasing access to the short-lived α-emitting radionuclide astatine-211 ( 211 At) has the potential to advance targeted α-therapeutic treatment of disease and to solve challenges facing the medical community. For example, there are numerous technical needs associated with advancing the use of 211 At in targeted α-therapy, e.g., improving 211 At chelates, developing more effective 211 At targeting, and characterizing in vivo 211 At behavior. There is an insufficient understanding of astatine chemistry to support these efforts. The chemistry of astatine is one of the least developed of all elements on the periodic table, owing to its limited supply and short half-life. Increasing access to 211 At could help address these issues and advance understanding of 211 At chemistry in general. We contribute here an extraction chromatographic processing method that simplifies 211 At production in terms of purification. It utilizes the commercially available Pre-Filter resin to rapidly (<1.5 h) isolate 211 At from irradiated bismuth targets (Bi decontamination factors ≥876 000), in reasonable yield (68-55%) and in a form that is compatible for subsequent in vivo study. We are excited about the potential of this procedure to address 211 At supply and processing/purification problems.

Advances in targeted α-therapies have increased the interest in actinium (Ac), whose chemistry is poorly defined due to scarcity and radiological hazards. Challenges associated with characterizing Ac 3+ chemistry are magnified by its 5f 0 6d 0 electronic configuration, which precludes the use of many spectroscopic methods amenable to small amounts of material and low concentrations (like EPR, UV-vis, fluorescence). In terms of nuclear spectroscopy, many actinium isotopes ( 225 Ac and 227 Ac) are equally "unfriendly" because the actinium α-, β-, and γ-emissions are difficult to resolve from the actinium daughters. To address these issues, we developed a method for isolating an actinium isotope ( 228 Ac) whose nuclear properties are well-suited for γ-spectroscopy. This four-step procedure isolates 228 Ra from naturally occurring 232 Th. The relatively long-lived 228 Ra ( t 1/2 = 5.75(3) years) radioisotope subsequently decays to 228 Ac. Because the 228 Ac decay rate [ t 1/2 = 6.15(2) h] is fast, 228 Ac rapidly regenerates after being harvested from the 228 Ra parent. The resulting 228 Ac generator provides frequent and long-term access (of many years) to the spectroscopically "friendly" 228 Ac radionuclide. We have demonstrated that the 228 Ac product can be routinely "milked" from this generator on a daily basis, in chemically pure form, with high specific activity and in excellent yield (∼95%). Hence, in the same way that developing synthesis routes to new starting materials has advanced coordination chemistry for many metals by broadening access, this 228 Ac generator has the potential to broaden actinium access for the inorganic community, facilitating the characterization of actinium chemical behavior.

A fundamental challenge in the design of bioresponsive (or bioactivated) Gd III -based magnetic resonance (MR) imaging probes is the considerable background signal present in the "preactivated" state that arises from outer-sphere relaxation processes. When sufficient concentrations of a bioresponsive agent are present (i.e., a detectable signal in the image), the inner- and outer-sphere contributions to r 1 may be misinterpreted to conclude that the agent has been activated, when it has not. Of the several parameters that determine the observed MR signal of an agent, only the electron relaxation time ( T 1e ) impacts both the inner- and outer-sphere relaxation. Therefore, strategies to minimize this background signal must be developed to create a near zero-background (or truly "off" state) of the agent. Here, we demonstrate that intramolecular magnetic exchange coupling when Gd III is coupled to a paramagnetic transition metal provides a means to overcome the contribution of second- and outer-sphere contributions to the observed relaxivity. We have prepared a series of complexes with the general formula LMLn(μ-O 2 CCH 3 )(O 2 CCH 3 ) 2 (M = Co, Cu, Zn). Solid-state magnetic susceptibility measurements reveal significant magnetic coupling between Gd III and the transition metal ion. Nuclear magnetic relaxation dispersion (NMRD) analysis confirms that the observed differences in relaxivity are associated with the modulation of T 1e at Gd III . These results clearly demonstrate that magnetic exchange coupling between Gd III and a transition metal ion can provide a significant decrease in T 1e (and therefore the relaxivity of Gd III ). This design strategy is being exploited to prepare new generations of preclinical bioresponsive MR imaging probes with near zero-background.

Misregulation of extracellular Ca 2+ can indicate bone-related pathologies. New, noninvasive tools are required to image Ca 2+ fluxes and fluorine magnetic resonance imaging ( 19 F-MRI) is uniquely suited to this challenge. Here, we present three, highly fluorinated peptide amphiphiles that self-assemble into nanoribbons in buffered saline and demonstrate these nanostructures can be programmed to change 19 F-NMR signal intensity as a function of Ca 2+ concentration. We determined these nanostructures show significant reduction in 19 F-NMR signal as nanoribbon width increases in response to Ca 2+ , corresponding to 19 F-MR image intensity reduction. Thus, these peptide amphiphiles can be used to quantitatively image biologically relevant Ca 2+ concentrations.