Actinium chelation and crystallization in a macromolecular scaffold.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39009580.
- Also identified by DOI 10.1038/s41467-024-50017-5 and PMC identifier 11251196.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Targeted alpha therapy (TAT) pairs the specificity of antigen targeting with the lethality of alpha particles to eradicate cancerous cells. Actinium-225 [<sup>225</sup>Ac; t<sub>1/2</sub> = 9.920(3) days] is an alpha-emitting radioisotope driving the next generation of TAT radiopharmaceuticals. Despite promising clinical results, a fundamental understanding of Ac coordination chemistry lags behind the rest of the Periodic Table due to its limited availability, lack of stable isotopes, and inadequate systems poised to probe the chemical behavior of this radionuclide. In this work, we demonstrate a platform that combines an 8-coordinate synthetic ligand and a mammalian protein to characterize the solution and solid-state behavior of the longest-lived Ac isotope, <sup>227</sup>Ac [t<sub>1/2</sub> = 21.772(3) years]. We expect these results to direct renewed efforts for <sup>225</sup>Ac-TAT development, aid in understanding Ac coordination behavior relative to other +3 lanthanides and actinides, and more broadly inform this element's position on the Periodic Table.
Medical subject headings
- Actinium
- Chelating Agents