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Actinium chelation and crystallization in a macromolecular scaffold

Author

Listed:
  • 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
    Michigan State University
    Michigan State University)

  • Stefan G. Minasian

    (Lawrence Berkeley National Laboratory)

  • Roland K. Strong

    (Fred Hutchinson Cancer Center)

  • Rebecca J. Abergel

    (Lawrence Berkeley National Laboratory
    University of California, Berkeley
    University of California, Berkeley)

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.

Suggested Citation

  • 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 & Rebecca J. Abergel, 2024. "Actinium chelation and crystallization in a macromolecular scaffold," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50017-5
    DOI: 10.1038/s41467-024-50017-5
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    References listed on IDEAS

    as
    1. Korey P. Carter & Katherine M. Shield & Kurt F. Smith & Zachary R. Jones & Jennifer N. Wacker & Leticia Arnedo-Sanchez & Tracy M. Mattox & Liane M. Moreau & Karah E. Knope & Stosh A. Kozimor & Corwin , 2021. "Structural and spectroscopic characterization of an einsteinium complex," Nature, Nature, vol. 590(7844), pages 85-88, February.
    2. Maryline G. Ferrier & Enrique R. Batista & John M. Berg & Eva R. Birnbaum & Justin N. Cross & Jonathan W. Engle & Henry S. La Pierre & Stosh A. Kozimor & Juan S. Lezama Pacheco & Benjamin W. Stein & S, 2016. "Spectroscopic and computational investigation of actinium coordination chemistry," Nature Communications, Nature, vol. 7(1), pages 1-8, November.
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