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

Abstract

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, T1 relaxation measurements were performed to study the effect of radiation on three GBCAs. GBCAs, gadoteric acid, gadobutrol and gadoxectic acid were investigated in a concentration range of 10-100mM. Measurements were performed on a 500MHz nuclear MR (NMR) spectrometer with a high-resolution inversion recovery sequence to determine T1. Samples were irradiated with 7 MV photons on an MR-linac to a total dose of 100Gy. 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. The overall measurement uncertainty was estimated to ±0.0053ms-1, corresponding to Gd3+(aq) detection levels 1%-1.5% or 1-4.5 micro molar at clinical GBCA dosage. No detectable differences in R1 were observed between irradiated and non-irradiated samples for any GBCA. 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.