Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study

Abstract

PURPOSEContrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) with gadolinium-based contrast agents (GBCAs) is standard of care for CNS imaging and diagnosis because of the visualization of lesions that cause blood–brain barrier breakdown. Gadobutrol is a macrocyclic GBCA with high concentration and high relaxivity. The objective of this study was to compare the safety and efficacy of gadobutrol 1.0 M vs unenhanced imaging and vs the approved macrocyclic agent gadoteridol 0.5 M at a dose of 0.1 mmol/kg bodyweight.MATERIALS AND METHODSProspective, multicenter, double-blind, crossover trial in patients who underwent unenhanced MRI followed by enhanced imaging with gadobutrol or gadoteridol. Three blinded readers assessed the magnetic resonance images. The primary efficacy variables included number of lesions detected, degree of lesion contrast-enhancement, lesion border delineation, and lesion internal morphology.RESULTSOf the 402 treated patients, 390 patients received study drugs. Lesion contrast-enhancement, lesion border delineation, and lesion internal morphology were superior for combined unenhanced/gadobutrol-enhanced imaging vs unenhanced imaging (P < 0.0001 for all). Compared with gadoteridol, gadobutrol was non-inferior for all primary variables and superior for lesion contrast-enhancement, as well as sensitivity and accuracy for detection of malignant disease. The percentage of patients with at least one drug-related adverse event was similar for gadobutrol (10.0%) and gadoteridol (9.7%).CONCLUSIONGadobutrol is an effective and well-tolerated macrocyclic contrast agent for MRI of the CNS. Gadobutrol demonstrates greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease than gadoteridol, likely because of its higher relaxivity.

Gadobutrol in India—A Comprehensive Review of Safety and Efficacy

“…A plethora of studies, including prospective head-to-head studies, have been performed on efficacy. For contrast-enhanced CNS, MRI publications of gadobutrol vs gadopentetate, 47 , 48 gadoterate, 49 and gadoteridol 50 , 51 are available. In all studies, certain efficacy parameters were superior to the comparators, be it conspicuity, 39 CNR, 40 overall preference and lesion contrast/enhancement, 49 or improved sensitivity and accuracy for detection of malignant lesions likely due to the high relaxivity.…”

“…They showed single dose of gadobutrol to be noninferior to a double dose of gadoteridol at detecting brain metastases. 50 Gutierrez et al 51 performed a phase 3 study with 390 patients concluding that gadobutrol demonstrates greater contrast enhancement and improved sensitivity and accuracy for detection of malignant disease than gadoteridol, likely because of its higher relaxivity.…”

The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study)

“…5 That differences in r1 relaxivity reflect differences in diagnostic efficacy is borne out by evidence from numerous large-scale intraindividual crossover studies. [1][2][3][4][8][9][10][11] These studies have shown that differences in SI enhancement and imaging performance reflect differences in r1 relaxivity and that the magnitude of the differences in SI enhancement a Comparisons based on the number of patients with both postdose T1SE images assessed and technically adequate: n ϭ 96 for reader 1, n ϭ 94 for reader 2, and n ϭ 95 for reader 3. Numbers in parentheses, except where noted, represent proportions of patients.…”

Diagnostic Performance of a 10-Minute Gadolinium-Enhanced Brain MRI Protocol Compared with the Standard Clinical Protocol for Detection of Intracranial Enhancing Lesions

“…The degree of enhancement was determined on the basis of a predefined 4-point scale: 0 (none), not visualized on 1 (or both) of the postcontrast sequences; 1 (subtle), faintly visualized on 3D sequences but better visualized on axial images (or vice versa); 2 (adequate), moderate degree of enhancement, equally seen in both 3D and axial sequences; and 3 (excellent), strong and sharply demarcated enhancement on both sequences. 20 Disagreements between readers were resolved by consensus review for presumed diagnoses and adjudicated by a third reader (P.S.) with 20 years of experience for the remaining variables.…”