Tripodal tris(hydroxypyridinone) ligands for immunoconjugate PET imaging with ⁸⁹Zr⁴⁺: comparison with desferrioxamine-B

Abstract

A tris(hydroxypyridinone) chelator coordinates the PET imaging isotope, 89Zr4+, rapidly and quantitatively under ambient conditions, but a 89Zr-labelled tris(hydroxypyridinone)-immunoconjugate is not stable to in vivo demetallation.

Di-macrocyclic terephthalamide ligands as chelators for the PET radionuclide zirconium-89

“…5 a – c Specific activities ( A s ) for each 89 Zr- 1 and 89 Zr- 2 were 997 MBq µmol −1 and 985 MBq µmol −1 respectively, and are in accord with the A s of other 89 Zr complexes reported in the literature. 3,5 a – c …”

“…2 f In order to overcome the potential issues of transchelation and non-specific accumulation in tissues, several studies have focused on modifying the conjugation chemistry needed to link DFO to antibodies or developing more effective chelators. 5 …”

“…These superior characteristics are believed to result from the ability of the TAM ligands to coordinate the oxophilic Zr 4+ ion in an octa-coordinated fashion using the 8 anionic oxygen donor atoms in the ligand architecture. 5 c Further studies such as acid and metal ion titration experiments, ligand competition binding assays, and single crystal X-ray crystallography will provide further insight into the mechanism of zirconium complexation and are currently underway in our laboratories.…”

“…Furthermore, 89 Zr- 1 demonstrated less bone retention than other 89 Zr-systems recently reported in the literature, and we speculate that this similarity to 89 Zr- DFO was a matter of effective and stable chelation in addition to efficient perfusion. 5 c …”

Iron speciation in natural waters by sequential injection analysis with a hexadentate 3-hydroxy-4-pyridinone chelator as chromogenic agent

“…So, to tackle this limitation, a more soluble and hexadentate 3-hydroxy-4-pyridinone ligand ( Fig. 1) [4][5][6] was explored in this work.…”