Zirconium-89 is a valuable nuclide for antibody-based radiotracers for diagnostic positron emission tomography (PET) imaging due to the advantageous match between its physical half-life of 78.41 h and the multi-day biological half-life of IgG antibodies. Within the realm of 89Zr-based PET tracers, the most widely used chelator for 89Zr4+ is desferrioxamine (DFO); however, the observed uptake of radioactivity in the bones of mice is evidence of in vivo release of 89Zr4+.1 A more robust chelation system for 89Zr4+ could eliminate the release of the bone-seeking 89Zr4+ cation in vivo and thus make for a safer PET tracer with reduced dose to non-target tissues. The first step in selecting an improved chelator is to understand the coordination chemistry of the Zr4+ cation. Zr4+ is a hard, oxophilic metal which requires a hard, oxygen donating ligand. DFO is a natural siderophore containing three hydroxamate groups, which works reasonably well with Zr4+. Other potentially interesting binding groups from natural siderophores include catechols and hydroxypyridinones. Herein, we examine the individual binding functionalities of hydroxamate, catechol, and hydroypyridinone groups as well as evaluate existing chelators containing these groups, namely DFO, 3,4,3-LICAM, and 3,4,3-(LI-1,2-HOPO), respectively. These last two ligands � 3,4,3-(LI-1,2-HOPO) and 3,4,3-LICAM � were selected from a library of published Pu chelators on the basis of the fact that Zr and Pu are known to have similar chemistries.2 The 3,4,3-(LI-1,2-HOPO) ligand in particular is shown to form a highly stable complex with 89Zr4+.

Evaluation of ligand binding groups for improved chelation of zirconium-89

248th National Meeting (2014)

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