Value of 1.0-M gadolinium chelates: review of preclinical and clinical data on gadobutrol

Abstract

Several preclinical and clinical studies with the first commercially available highly concentrated Gd-chelate gadobutrol (1 mol/l) are reviewed. Physicochemical, pharmacological, and pharmacokinetic properties, safety analysis, as well as experimental and clinical efficacy studies are highlighted in comparison with 0.5- M Gd-chelates. The 1-mol gadobutrol has been proven to be safe in an examined dose range from 0.04 up to 0.5 mmol/kg body weight (b.w.). Even in patients with chronic renal impairment, including hemodialysis, gadobutrol can safely be applied at doses up to 0.3 mmol/kg b.w. For contrast-enhanced MRI in the equilibrium phase, efficacy data analysis shows comparable results to other commercially available extracellular Gd-chelates with lower Gd-concentrations (0.5 M). Studies focused on the potential benefit of a tighter bolus, such as brain perfusion imaging using T2*-effects, document the superiority of a highly concentrated Gd contrast agent. For contrast-enhanced MRA, clinical studies are still ongoing; therefore, the ultimate potential of a more compact bolus, using 1- M Gd-chelates, for contrast-enhanced MRI, has still to be analyzed, especially for time-resolved magnetic resonance angiography.

Does Higher Gadolinium Concentration Play a Role in the Morphologic Assessment of Brain Tumors? Results of a Multicenter Intraindividual Crossover Comparison of Gadobutrol versus Gadobenate Dimeglumine (the MERIT Study)

“…20 Unlike gadobenate dimeglumine, gadobutrol does not interact to any appreciable extent with serum proteins and is excreted almost exclusively through the kidneys. 14,32,33 As a consequence, its R1 relaxivity in vivo is due entirely to the size and innate T1 shortening capacity of the gadobutrol molecule itself rather than to any augmentation of relaxivity and T1 shortening through interaction with serum albumin. Although reported relaxivity values vary slightly across publications depending on experimental conditions, 10,11,13 the results of well-conducted intraindividual comparative studies confirm that differences in relaxivity in vivo lead clinically to significantly better outcomes.…”

Diagnostic Yield of Double-Dose Gadobutrol in the Detection of Brain Metastasis: Intraindividual Comparison with Double-Dose Gadopentetate Dimeglumine

“…16,18,21 Gadobutrol had been proved to be a safe MR imaging contrast agent in patients with impaired renal function at doses of Յ0.3 mmol/L/kg of body weight. 22 So far, there have been no reports of nephrogenic systemic fibrosis in association with the administration of gadobutrol.…”

“…4,[6][7][8][9][10][11][12] Among the recently available MR imaging contrast media, gadobutrol (gadolinium-DO3A-butriol, Gadovist 1.0; Schering, Berlin, Germany) is the first commercially available 1.0-mol/L gadolinium chelate, a macrocyclic chelate not a linear one. [12][13][14][15][16][17] The lower osmolality and viscosity of gadobutrol enables the double-concentrated solution, which contains twice the amount of Gd chelate per volume. [12][13][14][15][16][17] The T1 relaxivity of gadobutrol is approximately 14%-27% higher than that of other 0.5-mol/L Gd chelates.…”

“…[12][13][14][15][16][17] The lower osmolality and viscosity of gadobutrol enables the double-concentrated solution, which contains twice the amount of Gd chelate per volume. [12][13][14][15][16][17] The T1 relaxivity of gadobutrol is approximately 14%-27% higher than that of other 0.5-mol/L Gd chelates. 18 Higher dose administration is known to be more effective in lesion detection, but consideration must be given to reducing the amount of gadolinium administered to the patient because of the risk of contrast-related reactions and nephrogenic systemic fibrosis.…”

Time‐resolved contrast‐enhanced three‐dimensional pulmonary MR‐angiography: 1.0 M gadobutrol vs. 0.5 M gadopentetate dimeglumine

“…Recently, new contrast agents offering an increased gadolinium concentration or a higher T1 relaxivity have been proposed for contrast-enhanced MRA (13)(14)(15)(16)(17). Due to the increased gadolinium concentration of 1.0 M gadobutrol, the injection volume can be halved compared to equimolar dosages of standard 0.5 M Gd-DTPA.…”