Abstract
Desferrioxamine (DFO) is the current “gold standard” chelator for 89Zr4+, which is used to label monoclonal antibodies for applications in immunopositron emission tomography. Recently, controversial data have been reported regarding the speciation and the stability of the complexes formed by DFO with Zr4+ in solution. To shed some light on this point, we studied the coordination properties in solution ofa chromophoric DFO derivative bearing a substituted pyrimidine residue (DFO–Pm) toward several metal ions (Zr4+, Cu2+, Zn2+, Mg2+, Ca2+, Na+, K+). Potentiometric titrations showed that DFO–Pm and pristine DFO form complexes with very similar stoichiometry and stability. DFO–Pm, which can consequently be taken as a model system for DFO, provides a photochemical response to metal coordination that can be used to further define the complexes formed. In the critical case of Zr4+, spectrophotometric measurements allowed the verification of the formation of 1:1 and 2:3 complexes that, together with 2:2 complexes form the coordination model that was obtained through the use of our potentiometric measurements. Additionally, mass spectrometry measurements verified the formation of 1:1 and 2:3 complexes and showed that 1:2 species can be easily generated through the fragmentation of the 2:3 species. In conclusion, the results obtained with DFO–Pm validate the complexation model of Zr4+/DFO composed of 1:1, 2:2, and 2:3 metal-to-ligand complexes. Convergences and conflicts with other works are addressed.
Highlights
IntroductionForm) for medical diagnostics using positron emission tomography (PET) and for cancer therapy
Zirconium-89 is one of the most studied radioactive isotopes for medical diagnostics using positron emission tomography (PET) and for cancer therapy
Site-specificity is governed by the target vector, which is covalently linked to a chelating unit that ensures metal ion sequestration, even at very low concentrations of the radioisotope (10–100 nM), thanks to the high thermodynamic and kinetic stability of the complex [1,2,3]
Summary
Form) for medical diagnostics using positron emission tomography (PET) and for cancer therapy. The application of this radioactive cation for in vivo imaging or therapy requires it is coordinated to a biologically active targeting molecule with marked site-specificity and high resistance to demetallation/transmetallation processes. Site-specificity is governed by the target vector (e.g., peptides, nucleotides, antibodies, etc.), which is covalently linked to a chelating unit that ensures metal ion sequestration, even at very low concentrations of the radioisotope (10–100 nM), thanks to the high thermodynamic and kinetic stability of the complex [1,2,3]. Desferrioxamine (DFO, Figure 1) is the current “gold standard” chelator for 89 Zr4+ [2].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
