Cross-bridged cyclams with bis(phosphinic acid) pendants for a fast Cu(II) complexation: towards efficient 64-Cu labeling


Cross-bridged cyclams with bis(phosphinic acid) pendants for a fast Cu(II) complexation: towards efficient 64-Cu labeling

Kubíček, V.; David, T.; Lubal, P.; Pietzsch, H.-J.; Hermanna, P.

Copper radioisotopes chelators are commonly based on macrocycles but they mostly suffer from in vivo instability, slow (not efficient) radiolabeling and low selectivity over competing ions. Cyclam derivatives offer high selectivity for Cu(II). Complexes of cross-bridged (CB-) cyclams are very stable in-vivo, however, their radiolabelling is not efficient.
We have found that bis(phosphinic acid) pendant arm (BPi) highly accelerate Cu(II) complexation.[1] It was also found, on Me3cyclam derivatives as model ligands, that phosphonic acid (Po) and bis(phosphorus acid) pendant arms are the most suitable ones for fast chelation.[2]
Chelators with BPi-like pendants on CB-cyclam (cb-BPC) were synthesized. Their complexation properties (structure, thermodynamics, formation/decomplexation kinetics) were investigated and analogous data were also obtained for known phosphorus chelators as cb-TE2P. All ligands are basic (last pKa>13.5) and form thermodynamically stable copper complexes. Other metal ion complexes are hardly formed in water. The Cu(II) complexes are formed quickly with some dependence on a kind of the pendant arms. Complexes of BPi containing chelators are significantly less kinetically inert than those of cb-TE2P but still much more inert than complexes of most of common chelators as DOTA. The phosphonic acid and BPi on CB-cyclams exhibit fast radiolabeling with 64-Cu even at room temperature and the labelled chelators are obtained with a high specific activity. These radiolabelling properties are not altered after conjugations.[3] The ligands can be suggested as a new chelator family for copper radioisotopes.

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    TeraChem 2018, 26.-29.09.2018, Brixen, Italien

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Publ.-Id: 28030