Investigation of the complexation ofnatZr(iv) and89Zr(iv) by hydroxypyridinones for the development of chelators for PET imaging applications.
Three hydroxypyridinone (HOPO) positional isomers - 1,2-HOPO (L1H) and its water soluble analogue (L1'H), 3,2-HOPO (L2H) and 3,4-HOPO (L3H) have been investigated for the complexation of Zr(iv). Potentiometric and UV-Vis spectrometric studies show a higher thermodynamic stability for the formation of Zr(L1')4in comparison with Zr(L2)4and Zr(L3)4as well as a higher kinetic inertness in competition studies with EDTA or Fe3+at a radiotracer concentration with89Zr. Besides the low pKaof L1H or L1'H (pKa= 5.01) in comparison with L2H and L3H (pKa= 8.83 and 9.55, respectively), the higher stability of Zr(L1')4can be attributed in part to the presence of the amide group next to the chelating oxygen that induces intramolecular H-bond and amide/π interactions that were observed by X-ray crystallography and confirmed by quantum chemical calculations. The data presented here indicate that the 1,2-HOPO L1' exhibits the best characteristics for Zr(iv) complexation. However, 3,2-HOPO and 3,4-HOPO patterns, if appropriately tuned, for instance with the addition of an amide group as in the 1,2-HOPO ligand, may also become interesting alternatives for the design of Zr(iv) chelators with improved characteristics for applications in nuclear imaging with89Zr.
CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France. francois.guerard@univ-nantes.fr and Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
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http://orcid.org/0000-0001-9795-2785
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Guérard
Université de Bretagne Occidentale, UMR-CNRS 6521 CEMCA, UFR des Sciences et Techniques, Brest, France.
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M
Beyler
Center for Molecular Modeling, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, USA.
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Lee
Université de Bretagne Occidentale, UMR-CNRS 6521 CEMCA, UFR des Sciences et Techniques, Brest, France.
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http://orcid.org/0000-0001-9364-788X
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Tripier
CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France. francois.guerard@univ-nantes.fr.
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JF
Gestin
Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
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Brechbiel