Distribution and clearance of retained gadolinium in the brain: differences between linear and macrocyclic gadolinium based contrast agents in a mouse model

Kartamihardja, Achmad Hussein Sundawa; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito

doi:10.1259/bjr.20160509

Cited by 39 publications

(47 citation statements)

References 33 publications

(45 reference statements)

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“…7,9,11 In several human 27,28 and animal studies, 23,33,34 the concentration of Gd in these brain structures has been shown to be significantly above background values. These observations raised the question about the underlying mechanism of Gd retention in the brain and the chemical species of the present Gd.…”

Section: Discussionmentioning

confidence: 99%

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents

Frenzel

Apte

Jošt³

et al. 2017

Invest Radiol

188

211

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Section: Discussionmentioning

confidence: 99%

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents

Frenzel

Apte

Jošt³

et al. 2017

Invest Radiol

188

211

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“…In a subsequent study with the same protocol, the same team demonstrated that, in the various brain areas of both renally impaired and naive mice treated with gadodiamide, the Gd clearance was limited over the time. 49 …”

Section: Discussionmentioning

confidence: 99%

Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats

et al. 2017

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ObjectivesThe purpose of this preclinical study was to investigate whether moderate chronic kidney disease is a factor in potentiating gadolinium (Gd) uptake in the brain.Materials and MethodsA comparative study was performed on renally impaired (subtotal nephrectomy) rats versus rats with normal renal function. The animals received 4 daily injections of 0.6 mmol Gd/kg a week for 5 weeks (cumulative dose of 12 mmol Gd/kg) of gadodiamide or saline solution. The MR signal enhancement in the deep cerebellar nuclei was monitored by weekly magnetic resonance imaging examinations. One week after the final injection, the total Gd concentration was determined by inductively coupled plasma mass spectrometry in different regions of the brain including the cerebellum, plasma, cerebrospinal fluid, parietal bone, and femur.ResultsAfter the administration of gadodiamide, the subtotal nephrectomy group presented a significantly higher T1 signal enhancement in the deep cerebellar nuclei and a major increase in the total Gd concentration in all the studied structures, compared with the normal renal function group receiving the same linear Gd-based contrast agent. Those potentiated animals also showed a pronounced hypersignal in the choroid plexus, still persistent 6 days after the last injection, whereas low concentration of Gd was found in the cerebrospinal fluid (<0.05 μmol/L) at this time point. Plasma Gd concentration was then around 1 μmol/L. Interestingly, plasma Gd was predominantly in a dissociated and soluble form (around 90% of total Gd). Total Gd concentrations in the brain, cerebellum, plasma, and bones correlated with creatinine clearance in both the gadodiamide-treated groups.ConclusionsRenal insufficiency in rats potentiates Gd uptake in the cerebellum, brain, and bones.

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“…With a median cumulative dose of 6.83 mmol/animal (range 0.54 to 16.65mmol/ animal) the clinical dataset shows much less cumulative GBCA dose as compared to published reports from human medicine [1] or animal experiments. [53] Even if a superior brain clearance of macrocyclic GBCAs over linear GBCAs is described [54,55] and all dogs of this study got a linear GBCA administration, the cumulative dose did not reach a visible level of hyperintensities after 2-3 administrations. We determined mean SI ratio differences between first and last MRI examination between 0.2% and 6.9% (range -12.5% to 13.8%), which was not significantly different from 0.…”

Section: Discussionmentioning

confidence: 74%

Gadolinium deposition in the brain of dogs after multiple intravenous administrations of linear gadolinium based contrast agents

et al. 2020

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Objective To determine the effect of a linear gadolinium-based contrast agent (GBCA) on the signal intensity (SI) of the deep cerebellar nuclei (DCN) in a retrospective clinical study on dogs after multiple magnetic resonance (MR) examinations with intravenous injections of gadodiamide and LA-ICP-MS analysis of a canine cerebellum after gadodiamide administration. Animals 15 client-owned dogs of different breeds and additionally 1 research beagle dog cadaver. Procedures In the retrospective study part, 15 dogs who underwent multiple consecutive MR imaging examinations with intravenous injection of linear GBCA gadodiamide were analyzed. SI ratio differences on unenhanced T1-weighted MR images before and after gadodiamide injections was calculated by subtracting SI ratios between DCN and pons of the first examination from the ratio of the last examination. Additionally, 1 research beagle dog cadaver was used for LA-ICP-MS (Laser ablation inductively coupled plasma mass spectrometry) analysis of gadolinium in the cerebellum as an add-on to another animal study. Descriptive and non-parametrical statistical analysis was performed and a p-value of < 0.05 was considered significant. Results No statistically significant differences of SI ratios, between DCN and pons, were detectable based on unenhanced T1-weighted MR images. LA-ICP-MS analyses showed between 1.5 to 2.5 μg gadolinium/g tissue in the cerebellum of the examined dog, 35 months after the last of 3 MRI examination with gadodiamide (two examinations at a dose of 1 x 0.1mmol/kg, last examination at a dose of 3 x 0.05mmol/kg).

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Distribution and clearance of retained gadolinium in the brain: differences between linear and macrocyclic gadolinium based contrast agents in a mouse model

Cited by 39 publications

References 33 publications

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents

Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats

Gadolinium deposition in the brain of dogs after multiple intravenous administrations of linear gadolinium based contrast agents

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