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

Faisal Mahmood*, Ulla Gro Nielsen, Christian Brandt Jørgensen, Carsten Brink, Henrik S. Thomsen, Rasmus Hvass Hansen


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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, T1 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 T1. 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 R1 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.

TidsskriftPhysics and Imaging in Radiation Oncology
Sider (fra-til)96-100
StatusUdgivet - jan. 2022

Bibliografisk note

Funding Information:
Authors are thankful to Benny Clifford Buthler, Department of Oncology, Odense University Hospital, for construction of the phantom for NMR tube irradiation, and colleagues at the Laboratory of Radiation Physics, Odense University Hospital, for technical assistance. This work was supported by a grant from Danish Cancer Society (Grant no. R231-A13852). Faisal Mahmood and Carsten Brink acknowledge support from MANTRA (New MAgNetic resonance Technology for Response Adapted radiotherapy), a Frontline research center based at Odense University Hospital, Denmark, and AgeCare (Academy of Geriatric Cancer Research), an international research collaboration based at Odense University Hospital, Denmark.

Publisher Copyright:
© 2022


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