The Radiochemistry of Zirconium

Heptadentate chelates for 89Zr-radiolabelling of monoclonal antibodies

“…The system is also complicated by the strong tendency of Zr 4+ ions to hydrolyse or form polymeric oxides by olation under aqueous (and often mildly basic) conditions. 22 Therefore, batch processes and ligand competition methods are required, which pose the problem of choosing an adequate competitor ligand that produces a thermodynamically stable, yet kinetically labile metal ion complex with a well-defined formation constant for use as a reference. Another challenge to the experimental determination of thermodynamic formation constants is that the titrations often require large amounts ( ca.…”

“…octadentate) ligands will form more stable complexes. 22 Rather, for these high denticity ligands where coordination number range from 6–8, the overall thermodynamic stability of the Zr 4+ complex is the result of electrostatic attractions between the ligand and the metal ion, as well as electrostatic repulsions induced between the donor atoms of the ligand and steric strain induced in the complex when wrapping the ligand around the central metal ion. Solvation factors also play a role.…”

“…Recent progress on aqueous-phase Zr-coordination chemistry has been reviewed extensively. [19][20][21][22] For new ligands to be useful in 89 Zr-radiochemistry, the compounds must have a reactive handle that allows bioconjugation to a protein (or other biologically active vector) of interest. Classical antibody functionalisation typically involves amide bond formation using N-hydroxysuccinimide (NHS) groups or thiourea synthesis from chemicals bearing benzyl isothiocyanate (NCS) groups.…”