Clinical use of gadobutrol for contrast-enhanced magnetic resonance imaging of neurological diseases

Kenneth T Cheng¹, Hannah Y Cheng², Kam Leung<sup>3

1</sup>Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA; ²Freelance Technical Writer, New Orleans, LA, USA; ³National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA

Abstract: Contrast-enhanced magnetic resonance imaging (CE-MRI) is an important clinical tool for diagnosing neurological diseases. The appropriate use of a suitable MRI contrast agent or contrast pharmaceutical is essential for CE-MRI to produce desirable diagnostic images. Currently, there are seven contrast agents (CAs) or pharmaceuticals approved for clinical imaging of the central nervous system (CNS) in the US, Europe, or Japan. All of the clinically approved CAs are water-soluble gadolinium-based contrast agents (GBCAs) which do not penetrate the CNS blood–brain barrier (BBB). These agents are used for imaging CNS areas without a BBB, or various pathologies, such as tumors and infection that break down the BBB and allow CAs to enter into the surrounding parenchyma. Clinically, GBCAs are most useful for detecting primary and secondary cerebral neoplastic lesions. Among these CNS GBCAs, gadobutrol (Gd-BT-DO3A, Gadovist™) is a neutral, nonionic, macrocyclic compound that showed promising results from clinical trials of CNS imaging. In comparison with other GBCAs, Gd-BT-DO3A has relatively high in vitro kinetic stability and r₁ relaxivity. Gd-BT-DO3A has been recently approved by the US Food and Drug Administration (FDA) in 2011 for CNS imaging. A review of available literature shows that Gd-BT-DO3A exhibits similar safety and clinical efficacy profiles to other GBCAs. Gd-BT-DO3A has the distinguishing feature that it is the only clinical agent commercially available in a formulation of 1.0 M concentration with a relatively higher in vitro T₁ shortening per unit volume than other clinical GBCAs which are only available in 0.5 M concentration. This double concentration of Gd-BT-DO3A may allow a relatively higher concentration of the agent to localize in the CNS and produce a better contrast enhancement at the same clinical dose as other GBCAs. Several recent published multicenter clinical trials appeared to support this potential advantage of Gd-BT-DO3A.

Keywords: Gadovist, Gd-BT-DO3A, CE-MRI, CNS imaging, MRI contrast agent, gadolinium