Journal Article

DKFZ-2025-02298

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Heavy Alkaline Earth Radiometals for Cancer Theranostics: Coordination and Radiochemistry of Radium-223 and Barium-131 with Kryptofix 22-Based Chelators.

Franchi, S. ; Asti, M. ; Blei, M. K. ; Pozzo, S. ; Madabeni, A. ; Graiff, C. ; Menegazzo, I. ; Volpato, F. ; Gentile, S. ; Orian, L. ; Mancin, F. ; Stadlbauer, S. ; Kopka, K.DKFZ* ; Mamat, C. ; Di Marco, V. ; Tosato, M.

2025
American Chemical Society Washington, DC

Abstract: The possibility of pairing the α-emitter 223Ra for targeted α therapy with the γ-emitter 131Ba for SPECT imaging could unlock novel theranostic options in cancer management. However, the lack of stable in vivo chelation for Ra2+/Ba2+ remains a key barrier to clinical use. Four macrocyclic chelators were herein developed by functionalizing 1,10-diaza-18-crown-6 (Kryptofix 22) with donor groups tailored to Ra2+/Ba2+: 2-pyridylphosphonic acid (macrophospho), malonic acid (macromal), catechol (macrocat), and 1,2-HOPO (macroHOPO). The thermodynamic and structural properties of their Ba2+ and Ra2+ complexes were explored in aqueous solution through potentiometry, NMR spectroscopy, X-ray crystallography and DFT calculations. Macromal gave the highest stability constant known so far for a 1:1 Ba2+-to-ligand fully deprotonated complex (logβ = 16.6), even higher than that of Ba2+-macropa, the current state-of-the-art chelator for 223Ra/131Ba. The experimental complex stability followed the order macromal > macropa ≫ macrophospho ∼ macroHOPO > macrocat. Concentration-, temperature-, pH-, and time-dependent radiolabeling were carried out using 223Ra derived from Xofigo residues and cyclotron-produced 131Ba. Although quantitative 223Ra/131Ba incorporation was not achieved, this work expands the scarce coordination chemistry and radiochemistry of the two heaviest alkaline earth (radio)metals.

Note: 2025 Nov 17;64(45):22422-22440

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Dresden (DD01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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