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.
OBJECTIVE
Contrast-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.


METHODS
Prospective, 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.


RESULTS
Of 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%).


CONCLUSIONS
Gadobutrol 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.
Neuroradiology Section, The University of Texas Health Science Center at San Antonio, TX, USA.
Juan E
JE
Gutierrez
Bayer Healthcare Pharmaceuticals, Montville, NJ, USA.
Martin
M
Rosenberg
Department of Neuroradiology, Werner-Forßmann Krankenhaus, Eberswalde, Germany.
Jörg
J
Seemann
Global Clinical Imaging Services, Bayer Pharma AG, Berlin, Germany.
Josy
J
Breuer
Bayer Healthcare Pharmaceuticals, Montville, NJ, USA.
Daniel
D
Haverstock
Bayer Healthcare Pharmaceuticals, Montville, NJ, USA.
Jacob
J
Agris
Bayer Healthcare Pharmaceuticals, Montville, NJ, USA.
Thomas
T
Balzer
Neuroradiology Department, Scientific Institute HSR Raffaele, Milan, Italy.
Nicoletta
N
Anzalone
contrast agent; gadobutrol; gadolinium; gadoteridol; magnetic resonance imaging