Species-dependent interaction of Gd-based contrast agents with humic substances

In this study, model experiments regarding species-dependent differences in the interaction of gadolinium-based contrast agents (GBCAs) with humic acids as potential binding partners in the aquatic environment are conducted. For this, the Gd content of different weight fractions obtained via ultracentrifugation of incubation solutions of humic acids with a linear (gadodiamide) and a macrocyclic GBCA (gadobutrol) were analyzed via inductively coupled plasma-mass spectrometry (ICP-MS). This enabled the fractionation of Gd-humic acid adducts and intact GBCAs, since Gd bound to macromolecules would be present in the macromolecular fraction of the filter residue while the low molecular weight Gd species can pass the filter with the filtrate. The Gd concentration in the different weight fractions was determined and a different reaction behavior for the examined GBCAs was observed. 73% of the total Gd amount was present in the macromolecular fraction of the linear GBCA compared to 0.41% in case of the macrocyclic GBCA. Speciation analysis of the macromolecular fractions by size exclusion chromatography-UV-ICP-MS confirmed that Gd-humic acid adducts were formed in case of the linear gadodiamide, but not with the macrocyclic gadobutrol. The findings of this study suggest that humic substance was able to react with the linear GBCA while the macrocyclic GBCA remained stable. Since free Gd ions are toxic, the question remains whether the humic acid bound Gd can be remobilized or if subsequent reactions with other molecules can take place. Furthermore, the persistence of macrocyclic GBCAs towards the humic substances indicates the potential accumulation of these compounds in the environment. However, more experiments regarding other binding partners and long term studies are needed to assess their ultimate fate after their release into the environment.