Zirconium-89 is useful for antibody-based radiotracers for medical positron emission tomography (PET) imaging due to its physical half-life of 78.41 hours matching the biological half-life of IgG antibodies which is on the order of a few days. The current widely used chelator for 89Zr is desferrioxamine (DFO), however there is evidence of in vivo release of 89Zr which can be observed as bone uptake in mice (Deri et al., 2013). A more robust chelation system for 89Zr could eliminate the release of the osteophillic 89Zr4+ cation in vivo and make for a safer PET tracer with less dose to non-target tissues. We have synthesized a pair of hydroxypyridinone (HOPO) and catechol based ligands for evaluation as potential chelators for 89Zr. The ligands 3,4,3-(LI-1,2-HOPO) and 3,4,3-LICAM were selected from a library of published Pu chelators (Gordon et al., 2003) on the basis of the fact that Zr and Pu are known to have similar chemistries. These ligands were synthesized using slightly modified procedures (Xu et al., 2002) in order to obtain extremely pure products suitable for tracer level experiments and radiolabeled with 89Zr. Additionally, the non-radioactive complexes were prepared and characterized using NMR, ESI-MS, and HPLC. The identity of the 89Zr complex of 3,4,3-(LI-1,2-HOPO) has been confirmed through HPLC co-elution with its non-radioactive analogue. The 89Zr-ligand complex demonstrates high labeling efficiency and comparable stability to 89Zr-DFO. Radiolabeling of 3,4,3-(LI-1,2-HOPO) initially results in two distinct species, one of which converts to the other over time. The precise nature of these two species is presently being investigated. The 3,4,3-LICAM ligand has been synthesized and the evaluation of its radiolabeling properties is currently underway.

Alternative chelators for zirconium-89: Radiolabeling and evaluation of 3,4,3-(LI-1,2-HOPO) and 3,4,3-LICAM

246th National Meeting (2013)

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