A UV-Vis method for investigation of gallium() complexation kinetics with NOTA and TRAP chelators: advantages, limitations and comparison with radiolabelling

An easy and cheap method for measurement of Ga III complexation kinetics was developed. The method is based on UV-Vis quantification of non-complexed chelators after the addition of Cu II ions at individual time points. The method was evaluated using established ligands, H 3 nota and H 6 notP Pr , and was utilized to study the kinetics of Ga III complexation with four new symmetric derivatives of 1,4,7-triazacyclononane bearing methylphosphonate/phosphinate pendant arms - TRAP ligands. Chelators bearing ethoxy groups (H 3 L 1 ) or 2,2,2-trifluoroethyl groups (H 3 L 2 ) on the phosphorus atoms showed fast formation ( t 99% = 21 and 10 min, respectively, at pH 2.0) and efficient radiolabelling which were comparable to the previously reported chelators bearing the 2-carboxyethyl group (H 6 notP Pr ). Chelators bearing ( N , N -dibenzyl-amino)methyl (H 3 L 3 ) and aminomethyl (H 3 L 4 ) substituents showed a significantly slower complexation ( t 99% = 4.4 and 3.6 h, respectively, at pH 2.0) and inefficient radiolabelling, mainly at room temperature or low pH. This was caused by protonation of the amino groups of the pendant arms leading to coulombic repulsion between the Ga III ion and the positively charged protonated amines. The trends in complexation rates determined by the UV-Vis method correlated well with the results of the 68 Ga radiolabelling study. An easy and cheap method for UV-Vis measurement of Ga III complexation kinetics with macrocyclic ligands was developed and validated. The complexation kinetics of NOTA and its phosphinate analogues was compared with 68 Ga labelling.