Safety of gadolinium based contrast agents in magnetic resonance imaging-guided radiotherapy - An investigation of chelate stability using relaxometry

Background and purpose: With the introduction of hybrid magnetic resonance linacs (MR-linac), improved imaging has enabled daily treatment adaptation. However, the use of gadolinium based contrast agents (GBCAs) is desired to further improve MR image contrast. GBCAs are in the form of a non-toxic metalorganic gadolinium complex, but toxic un-chelated aqueous gadolinium(III), Gd3+(aq), can be released in patients if the organic ligand is degraded by the radiation. In this study, T-1 relaxation measurements were performed to study the effect of radiation on three GBCAs. Materials and methods: GBCAs, gadoteric acid, gadobutrol and gadoxectic acid were investigated in a concentration range of 10-100 mM. Measurements were performed on a 500 MHz nuclear MR (NMR) spectrometer with a high-resolution inversion recovery sequence to determine T-1. Samples were irradiated with 7 MV photons on an MR-linac to a total dose of 100 Gy. The lower detection limit of Gd3+(aq) was established by estimating the overall measurement uncertainty and comparing to corresponding changes in R1 when replacing chelated Gd3+ with gadolinium nitrate at predefined percentages. Results: The overall measurement uncertainty was estimated to +/- 0.0053 ms(-1), corresponding to Gd3+(aq) detection levels 1%-1.5% or 1-4.5 micro molar at clinical GBCA dosage. No detectable differences in R-1 were observed between irradiated and non-irradiated samples for any GBCA. Conclusions: This study did not find any measurable degradation of GBCAs due to irradiation with high-energy X-rays, however, in-vivo investigations are needed to provide the clinical basis for safe use of contrast agents in a radiotherapy workflow.