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Issue 7, 2018
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Structure and properties of DOTA-chelated radiopharmaceuticals within the 225Ac decay pathway

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Abstract

The successful delivery of toxic cargo directly to tumor cells is of primary importance in targeted (α) particle therapy. Complexes of radioactive atoms with the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelating agent are considered as effective materials for such delivery processes. The DOTA chelator displays high affinity to radioactive metal isotopes and retains this capability after conjugation to tumor targeting moieties. Although the α-decay chains are well defined for many isotopes, the stability of chelations during the decay process and the impact of released energy on their structures remain unknown. The radioactive isotope 225Ac is an α-particle emitter that can be easily chelated by DOTA. However, 225Ac has a complex decay chain with four α-particle emissions during decay of each radionuclide. To advance our fundamental understanding of the consequences of α-decay on the stability of tumor-targeted 225Ac–DOTA conjugate radiopharmaceuticals, we performed first principles calculations of the structure, stability, and electronic properties of the DOTA chelator to the 225Ac radioactive isotope, and the initial daughters in the decay chain, 225Ac, 221Fr, 217At and 213Bi. Our calculations show that the atomic positions, binding energies, and electron localization functions are affected by the interplay between spin–orbit coupling, weak dispersive interactions, and environmental factors. Future empirical measurements may be guided and interpreted in light of these results.

Graphical abstract: Structure and properties of DOTA-chelated radiopharmaceuticals within the 225Ac decay pathway

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Publication details

The article was received on 28 Mar 2018, accepted on 05 Jun 2018 and first published on 06 Jun 2018


Article type: Research Article
DOI: 10.1039/C8MD00170G
Citation: Med. Chem. Commun., 2018,9, 1155-1163
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    Structure and properties of DOTA-chelated radiopharmaceuticals within the 225Ac decay pathway

    A. R. Khabibullin, A. Karolak, M. M. Budzevich, M. L. McLaughlin, D. L. Morse and L. M. Woods, Med. Chem. Commun., 2018, 9, 1155
    DOI: 10.1039/C8MD00170G

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