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

合成和评价含羟肟酸基团的二氮杂冠醚骨架螯合剂用于Zr-89螯合化学

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Abstract

Zirconium-89 ((89)Zr) 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 (89)Zr. 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 (89)Zr under mild conditions. The (89)Zr-labeled DA-18C6-BHA complex remained stable in human serum and apotransferrin for 7 days. When challenged with excess EDTA solution, (89)Zr-labeled DA-18C6-BHA was shown to hold (89)Zr without losing considerable radioactivity to EDTA. The (89)Zr-labeled DA-18C6-BHA complex displayed high complex stability in normal mice as evidenced by low bone uptake.

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