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

Abstract

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

Keywords: Chelator; PET Imaging; Zr-89.