Gadolinium retention in a rat model of subtotal renal failure: are there differences among macrocyclic GBCAs?

Abstract

Background Gd levels are higher in tissues of animals with compromised renal function, but studies to compare levels after exposure to different macrocyclic gadolinium-based contrast agents (GBCAs) are lacking. We compared Gd levels in tissues of subtotally nephrectomised (SN) rats after repeated exposure to macrocyclic GBCAs. Methods Sprague–Dawley SN male rats (19 per group) received 16 injections of gadoteridol, gadobutrol, or gadoterate meglumine at 0.6 mmol Gd/kg 4 times/weeks over 4 weeks. A control group of healthy male rats (n = 10) received gadoteridol at the same dosage. Plasma urea and creatinine levels were monitored. Blood, cerebrum, cerebellum, liver, femur, kidney(s), skin and peripheral nerves were harvested for Gd determination by inductively coupled plasma-mass spectrometry at 28 and 56 days after the end of treatment. Results Plasma urea and creatinine levels were roughly twofold higher in SN rats than in healthy rats at all timepoints. At day 28, Gd levels in the peripheral nerves of gadobutrol- or gadoterate-treated SN animals were 5.4 or 7.2 times higher than in gadoteridol-treated animals (p < 0.001). Higher Gd levels after administration of gadobutrol or gadoterate versus gadoteridol were also determined in kidneys (p ≤ 0.002), cerebrum (p ≤ 0.001), cerebellum (p ≤ 0.003), skin (p ≥ 0.244), liver (p ≥ 0.053), and femur (p ≥ 0.271). At day 56, lower Gd levels were determined both in SN and healthy rats for all GBCAs and tissues, except the femur. Conclusions Gd tissue levels were lower following gadoteridol exposure than following gadobutrol or gadoterate exposure.

Ten years of gadolinium retention and deposition: ESMRMB-GREC looks backward and forward

“…In comparative studies in rats, macrocyclic GBCA led to measurable Gd concentrations at 1–5 weeks after administration, which were lower for gadoteridol compared to gadoterate and gadobutrol, independent of renal function [ 46 ]. The GBCA wash-out led to a 3–5-fold reduction from 1 to 5 weeks which was more rapid for gadoteridol.…”

“…In animal studies, residual Gd is also present in abdominal tissue samples [ 46 , 62 – 66 ]. While deposition in the brain was only 2–7 μg Gd/g tissue, the amounts in other organs were much higher for kidney, liver, and spleen.…”

“…In subtotally nephrectomised rats, higher Gd levels 28 days after administration of gadobutrol or gadoterate versus gadoteridol were determined in the kidneys and liver. After 56 days, lower Gd levels were determined for all GBCA [ 46 ].…”