Evaluation Of Macrocyclic Hydroxyisophthalamide Ligands As Chelators For Zirconium-89

The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. Herein we report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. While both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of Zr-89-1 required elevated temperature and an increased reaction time. Zr-89-1 was more stable than Zr-89-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. Differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligandoptimization is necessary to enhance Zr-89 chelation.