Synthesis and evaluation of Diaza-Crown Ether-Backboned chelator containing hydroxamate groups for Zr-89 chelation chemistry

Zirconium-89 (Zr-89) has been explored for molecularly targeted positron emission tomography (PET) imaging of various diseases. We synthesized and evaluated a novel chelator (DA-18C6-BHA) for Zr-89. The new chelator is structured on a macrocyclic backbone (1,10-diaza-18-crown-6) and contains hydroxamates as acyclic donor groups. The new chelator ((DA-18C6-BHA) was rapidly labeled with Zr-89 under mild conditions. The Zr-89-labeled DA-18C6-BHA complex remained stable in human serum and apotransferrin for 7 days. When challenged with excess EDTA solution, Zr-89-labeled DA-18C6-BHA was shown to hold Zr-89 without losing considerable radio-activity to EDTA. The Zr-89-labeled DA-18C6-BHA complex displayed high complex stability in normal mice as evidenced by low bone uptake.