The potential toxic impact of different gadolinium-based contrast agents combined with 7-T MRI on isolated human lymphocytes

Abstract

BackgroundTo investigate a potentially amplifying genotoxic or cytotoxic effect of different gadolinium-based contrast agents (GBCAs) in combination with ultra-high-field 7-T magnetic resonance imaging (MRI) exposure in separated human peripheral blood lymphocytes.MethodsThis in vitro study was approved by the local ethics committee and written informed consent was obtained from all participants. Isolated lymphocytes from twelve healthy donors were incubated with gadobutrol, gadoterate meglumine, gadodiamide, gadopentetate dimeglumine, or gadoxetate either alone or combined with 7-T MRI (1 h). Deoxyribonucleic acid (DNA) double-strand breaks were assessed 15 min after MRI exposure by automated γH2AX foci quantification. Cytotoxicity was determined at later endpoints by Annexin V/propidium iodide apoptosis assay (24 h) and [3H]-thymidine proliferation test (72 h). As a reference, lymphocytes from four different donors were exposed analogously to iodinated contrast agents (iomeprol, iopromide) in combination with computed tomography.ResultsBaseline γH2AX levels (0.08 ± 0.02 foci/cell) were not significantly (p between 0.135 and 1.000) enhanced after administration of GBCAs regardless of MRI exposure. In contrast to the two investigated macrocyclic GBCAs, lymphocytes exposed to the three linear GBCAs showed a dose-dependent increase in apoptosis (maximum 186% of unexposed control, p < 0.001) and reduced proliferation rate (minimum 0.7% of unexposed control, p < 0.001). However, additional 7-T MRI co-exposure did not alter GBCA-induced cytotoxicity.ConclusionsExposure of lymphocytes to different GBCAs did not reveal significant induction of γH2AX foci, and enhanced cytotoxicity was only observed in lymphocytes treated with the linear GBCAs used in this study, independent of additional 7-T MRI co-exposure.