Thermodynamics on the first hydrolysis reaction of dysprosium and holmium in aqueous solutions: potentiometry and calorimetry

The potential release of Dy 3+ and Ho 3+ ions from 166 Dy/ 166 Ho or 166 Ho microspheres during radionuclide therapy poses a radiotoxicological risk, as their biochemical behavior is governed by hydrolysis. This study presents a comprehensive thermodynamic investigation of the first hydrolysis step of Dy 3+ and Ho 3+ in aqueous solutions, employing potentiometry and isothermal titration calorimetry (ITC). We report, for the first time, the direct calorimetric determination of the hydrolysis enthalpies for these lanthanides. Our results identify two viable models for the first hydrolysis step – monomeric [Ln (OH)] 2+ and dimeric [Ln 2 (OH) 2 ] 4+ species – with thermodynamic parameters quantified for both. The hydrolysis reactions are endothermic and predominantly electrostatic. Under simulated physiological conditions (pH 7–8), 15–20 % of Dy 3+ and 22–27 % of Ho 3+ are hydrolyzed. A key practical implication is that hydrolysis is thermodynamically disfavored at low temperatures, suggesting that refrigerated storage of microspheres can minimize ion release. These findings provide critical thermodynamic benchmarks for predicting lanthanide speciation and recommend storing therapeutic microspheres at low temperatures to suppress hydrolysis.