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Gadolinium-based Contrast Agent Biodistribution and Speciation in Rats.
Mariane Le Fur1, Brianna F Moon1, Iris Y Zhou1
1From the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (M.L.F., B.F.M., I.Y.Z., S.Z., A.B., N.J.R., I.A., P.P., D.I.G., P.C.), Department of Urology (A.S.F.), and Department of Pathology (I.A.R., I.D.A.L.H., L.P.H.), Massachusetts General Hospital and Harvard Medical School, 149 13th St, Charlestown, MA 02129; Institute for Innovation in Imaging, Massachusetts General Hospital, Charlestown, Mass (M.L.F., B.F.M., I.Y.Z., S.Z., A.B., N.J.R., I.A., P.P., P.C.); Harvard-MIT Health Sciences and Technology, Cambridge, Mass (D.I.G.); Bioengineering Department, Universidad Carlos III de Madrid, Madrid, Spain (D.I.G.); Department of Chemistry and Biochemistry, University of Arizona, Tucson, Ariz (A.V.A.); and Trace Element Analysis Laboratory, Dartmouth College, Hanover, NH (B.P.J.).
Gadolinium-based contrast agents (GBCAs) show varying retention in rat kidneys, with gadoteridol demonstrating the lowest retention. T1-weighted MRI is not sensitive for detecting residual gadolinium in the kidney cortex.
Area of Science:
- Radiology
- Pharmacokinetics
- Medical Imaging
Background:
- Gadolinium retention in organs occurs even in patients with normal renal function.
- The biodistribution and speciation of residual gadolinium are not fully understood.
Purpose of the Study:
- To compare the pharmacokinetics, distribution, and speciation of four gadolinium-based contrast agents (GBCAs) in healthy rats.
- To evaluate gadolinium retention using MRI, mass spectrometry, elemental imaging, and EPR spectroscopy.
Main Methods:
- 32 rats received one of four GBCAs (gadoterate, gadoteridol, gadobutrol, or gadobenate) for 10 days.
- Kidney imaging (T1-weighted, R2* maps) and ex vivo analysis (mass spectrometry, elemental imaging, EPR spectroscopy) were performed at multiple time points.
- Data were analyzed using ANOVA, Kruskal-Wallis, and correlation analyses.
Main Results:
- The kidney cortex showed the highest gadolinium retention for all GBCAs at 17 days post-injection.
- Gadoteridol exhibited the lowest retention levels compared to other GBCAs.
- Renal cortex R2* values correlated with ex vivo gadolinium concentrations, but T1-weighted MRI signal intensity did not.
Conclusions:
- Gadoteridol administration resulted in the lowest gadolinium retention among the tested macrocyclic GBCAs.
- The kidney cortex retains the highest concentration of gadolinium, but T1-weighted MRI is insensitive to its detection in this tissue.
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