Assessment of Gadobutrol Safety in Combination with Ionizing Radiation Using a Preclinical MRI-Guided Radiotherapy Model

Radiat Res. 2021 Mar 1;195(3):230-234. doi: 10.1667/RADE-20-00199.1.

Abstract

MR-linac technology enhances the precision of therapeutic radiation by clarifying the tumor-normal tissue interface and provides the potential for adaptive treatment planning. Accurate delineation of tumors on diagnostic magnetic resonance imaging (MRI) frequently requires gadolinium-based contrast agents (GBCAs). Despite generally being considered safe, previous literature suggests that GBCAs are capable of contrast-induced acute kidney injury (AKI). It is unclear if the risk for AKI is enhanced when GBCAs are administered concurrently with ionizing radiotherapy. During irradiation, gadolinium may be liberated from its chelator which may induce AKI. The goal of this work was to determine if radiation combined with GBCAs increased the incidence of AKI. Using a preclinical MRI-guided irradiation system, where MRI acquisitions and radiation delivery are performed in rapid succession, tumor-bearing mice with normal kidney function were injected with GBCA and treated with 2, 8 or 18 Gy irradiation. Renal function was assessed on days three and seven postirradiation to assess for AKI. No clinically relevant changes in blood urea nitrogen and creatinine were observed in any combination of GBCA and radiation dose. From these data, we conclude that GBCA in combination with radiation does not increase the risk for AKI in mice. Additional investigation of multiple doses of GBCA administered concurrently with irradiation is warranted to evaluate the risk of chronic kidney injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / diagnostic imaging*
  • Acute Kidney Injury / physiopathology
  • Animals
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / pathology
  • Brain / radiation effects
  • Contrast Media / adverse effects
  • Contrast Media / pharmacology*
  • Disease Models, Animal
  • Gadolinium / adverse effects
  • Gadolinium / pharmacology
  • Humans
  • Kidney / diagnostic imaging
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / radiation effects
  • Magnetic Resonance Imaging
  • Mice
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / pharmacology*
  • Radiation, Ionizing*
  • Radiotherapy, Image-Guided / adverse effects
  • Radiotherapy, Image-Guided / methods

Substances

  • Contrast Media
  • Organometallic Compounds
  • gadobutrol
  • Gadolinium