Differences in gadolinium retention after repeated injections of macrocyclic MR contrast agents to rats.

PURPOSE: To compare the levels of gadolinium in the blood, cerebrum, cerebellum, liver, femur, kidneys, and skin after multiple exposure of rats to the macrocyclic gadolinium-based contrast agents (GBCAs) gadoterate, gadobutrol, and gadoteridol. MATERIALS AND METHODS: Fifty male Wistar Han rats were randomized to three exposure groups (n = 15 per group) and one control group (n = 5). Animals in the exposure groups received a total of 20 GBCA administrations (four administrations per week for 5 consecutive weeks) at a dose of 0.6 mmol/kg bodyweight. After a 28-day recovery period animals were sacrificed and the blood and tissues harvested for determination of gadolinium (Gd) levels. Gd determination was performed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: After 28 days' recovery no Gd was found in the blood, liver, or skin of any animal in any group. Significantly lower levels of Gd were noted with gadoteridol compared to gadoterate and gadobutrol in the cerebellum (0.150 ± 0.022 vs. 0.292 ± 0.057 and 0.287 ± 0.056 nmol/g, respectively; P < 0.001), cerebrum (0.116 ± 0.036 vs. 0.250 ± 0.032 and 0.263 ± 0.045 nmol/g, respectively; P < 0.001), and kidneys (25 ± 13 vs. 139 ± 88 [P < 0.01] and 204 ± 109 [P < 0.001], respectively). Higher levels of Gd were noted in the femur (7.48 ± 1.37 vs. 5.69 ± 1.75 and 8.60 ± 2.04 nmol/g, respectively) with significantly less Gd determined for gadoterate than for gadobutrol (P < 0.001) and gadoteridol (P < 0.05). CONCLUSION: Differences exist between macrocyclic agents in terms of their propensity to accumulate in tissues. The observed differences in Gd concentration point to differences in GBCA washout rates in this setting and in this experimental model, with gadoteridol being the GBCA that is most efficiently removed from both cerebral and renal tissues. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:746-752.

Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats.

OBJECTIVES: The purpose of this study was to compare Gd levels in rat tissues after cumulative exposure to four commercially available macrocyclic gadolinium-based contrast agents (GBCAs). METHODS: Sixty-five male Sprague-Dawley rats were randomized to four exposure groups (n = 15 per group) and one control group (n = 5). Animals in each exposure group received 20 GBCA administrations (four per week of ProHance®, Dotarem®, Clariscan™, or Gadovist® for 5 consecutive weeks) at a dose of 0.6 mmol/kg bodyweight. After 28-days' recovery, animals were sacrificed and tissues harvested for Gd determination by inductively coupled plasma-mass spectroscopy (ICP-MS). Histologic assessment of the kidney tissue was performed for all animals. RESULTS: Significantly (p ≤ 0.005; all evaluations) lower Gd levels were noted with ProHance® than with Dotarem®, Clariscan™, or Gadovist® in all soft tissue organs: 0.144 ± 0.015 nmol/g vs. 0.342 ± 0.045, 0.377 ± 0.042, and 0.292 ± 0.047 nmol/g, respectively, for cerebrum; 0.151 ± 0.039 nmol/g vs. 0.315 ± 0.04, 0.345 ± 0.053, and 0.316 ± 0.040 nmol/g, respectively, for cerebellum; 0.361 ± 0.106 nmol/g vs. 0.685 ± 0.330, 0.823 ± 0.495, and 1.224 ± 0.664 nmol/g, respectively, for liver; 38.6 ± 25.0 nmol/g vs. 172 ± 134, 212 ± 121, and 294 ± 127 nmol/g, respectively, for kidney; and 0.400 ± 0.112 nmol/g vs. 0.660 ± 0.202, 0.688 ± 0.215, and 0.999 ± 0.442 nmol/g, respectively, for skin. No GBCA-induced macroscopic or microscopic findings were noted in the kidneys. CONCLUSIONS: Less Gd is retained in the brain and body tissues of rats 28 days after the last exposure to ProHance® compared to other macrocyclic GBCAs, likely due to unique physico-chemical features that facilitate more rapid and efficient clearance.

Cyclic carbonate formation from carbon dioxide and oxiranes in tetrabutylammonium halides as solvents and catalysts.

[reaction: see text] Epoxides dissolved in molten tetralkylammonium salts bearing halides as counterions are converted into cyclic carbonates under atmospheric pressure of carbon dioxide. The reaction rate depends on the nucleophilicity of the halide ion as well as the structure of the cation.