Actinium chelation and crystallization in a macromolecular scaffold

Jennifer N. Wacker, Joshua J. Woods, Peter B. Rupert, Appie Peterson, Marc Allaire, Wayne W. Lukens, Alyssa N. Gaiser, Stefan G. Minasian, Roland K. Strong () and Rebecca J. Abergel ()
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Jennifer N. Wacker: Lawrence Berkeley National Laboratory
Joshua J. Woods: Lawrence Berkeley National Laboratory
Peter B. Rupert: Fred Hutchinson Cancer Center
Appie Peterson: Lawrence Berkeley National Laboratory
Marc Allaire: Lawrence Berkeley National Laboratory
Wayne W. Lukens: Lawrence Berkeley National Laboratory
Alyssa N. Gaiser: Lawrence Berkeley National Laboratory
Stefan G. Minasian: Lawrence Berkeley National Laboratory
Roland K. Strong: Fred Hutchinson Cancer Center
Rebecca J. Abergel: Lawrence Berkeley National Laboratory

Nature Communications, 2024, vol. 15, issue 1, 1-8

Abstract: Abstract Targeted alpha therapy (TAT) pairs the specificity of antigen targeting with the lethality of alpha particles to eradicate cancerous cells. Actinium-225 [225Ac; t1/2 = 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, 227Ac [t1/2 = 21.772(3) years]. We expect these results to direct renewed efforts for 225Ac-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.

Date: 2024
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DOI: 10.1038/s41467-024-50017-5

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