Preparation of an Actinium-228 Generator

Abstract

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 Ac3+ chemistry are magnified by its 5f06d0 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 (225Ac and 227Ac) 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 (228Ac) whose nuclear properties are well-suited for γ-spectroscopy. This four-step procedure isolates 228Ra from naturally occurring 232Th. The relatively long-lived 228Ra (t 1/2 = 5.75(3) years) radioisotope subsequently decays to 228Ac. Because the 228Ac decay rate [t 1/2 = 6.15(2) h] is fast, 228Ac rapidly regenerates after being harvested from the 228Ra parent. The resulting 228Ac generator provides frequent and long-term access (of many years) to the spectroscopically “friendly” 228Ac radionuclide. We have demonstrated that the 228Ac 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 228Ac generator has the potential to broaden actinium access for the inorganic community, facilitating the characterization of actinium chemical behavior.

Capturing an elusive but critical element: Natural protein enables actinium chemistry

“…Little information has been published on the recovery of 228 Ac 3+ from macroscopic amounts of 232 Th 4+ , besides a recent liquid-liquid extraction method performed in concentrated HNO 3 media ( 36 ), and an ion-exchange protocol including >30 steps (fig. S9) ( 37 ), which we deemed impractical for such a short-lived radioisotope. The liquid-liquid extraction method developed by Kazakov and co-workers ( 36 ) consists of a multistage process where a 232 Th(IV) salt is first dissolved in 4 M HNO 3 , and then three consecutive liquid-liquid extraction batches are performed using the extractant di-(2-ethylhexyl)phosphoric acid and toluene as diluent (each batch necessitating three steps: mixing, centrifugation, and phase separation using a funnel) followed by two column chromatography separations and an evaporation to dryness and redissolution step (fig.…”

Protein-Based Platform for Purification, Chelation, and Study of Medical Radiometals: Yttrium and Actinium

“…228 Ra regenerates 228 Ac within ~30 hours, due to secular equilibrium, so it represents a potential 228 Ra/ 228 Ac generator (Figure S7). Little information has been published on the recovery of 228 Ac from macroscopic amounts of 232 Th, besides a recent liquid-liquid extraction method performed in concentrated HNO3 media 32 , and an ion-exchange protocol including >30 steps 33 (Figure S8), which we deemed impractical for such a short-lived radioisotope. Additionally, we experimentally observed that the activity of 228 Ra/ 228 Ac solutions increases after ~28 days due to reformation of 228 Th from 228 Raa phenomenon predicted by the Bateman equation but overlooked in the literaturerendering previously proposed 228 Ra/ 228 Ac generators rapidly inoperable (Figure S6).…”

Advancing understanding of actinide(iii) (Ac, Am, Cm) aqueous complexation chemistry

“…Hence, Ac 3+ purifications combined the DGA extraction chromatography with anion exchange chromatography using AG-1X8 resin. 67 …”