Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Dec 23;27(1):58.
doi: 10.3390/molecules27010058.

How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo

Quyen N Do  1 , Robert E Lenkinski  1 , Gyula Tircso  2 , Zoltan Kovacs  3
Affiliations
Review

How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo

Quyen N Do et al. Molecules. .

Abstract

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.

Keywords: T1 hyperintensity; gadolinium deposition; gadolinium-based contrast agents; kinetic inertness; thermodynamic stability.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The two standard ligand scaffolds used in clinically approved GBCAs. (DTPA = diethylenetriaminepentaacetic acid or pentetic acid; DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid or tetraxetan).
Figure 2
Figure 2
FDA-approved GBCAs utilized in the clinical practice.
Figure 3
Figure 3
Structure of Gadopiclenol, a macrocyclic pyclen-based contrast agent.
Figure 4
Figure 4
At 1 Tesla, GdPO4 phantom shows enhancement at the solution solid interface. (a) T1-weighted spin echo image (TR/TE = 350/13.1 ms), (b) T2-weighted spin echo image (TR/TE = 1600/120 ms), (c) A photo of the microcentrifuge tubes making up GdPO4 phantom: the tube on the right contains deionized (DI) water, the one on the left contains a GdPO4 precipitate in DI water after centrifugation.
See this image and copyright information in PMC

References

    1. Balzer T., Bayer HealthCare Pharmaceuticals Inc. Medical Imaging Drugs Advisory Committee (MIDAC) U.S. Food & Drug Administration; Silver Spring, MD, USA: 2017. Presence of Gadolinium (Gd) in the brain and body.
    1. GE Healthcare Omniscan (Gadodiamide). U.S. Food and Drug Administration. [(accessed on 21 December 2021)];2010 Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020123s037lbl.pdf.
    1. Bayer HealthCare Pharmaceuticals Gadavist (Gadobutrol). U.S. Food and Drug Administration. [(accessed on 21 December 2021)];2019 Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/201277s017lbl.pdf.
    1. Lantheus Medical Imaging, Inc. Ablavar (Gadofosveset Trisodium). U.S. Food and Drug Administration. [(accessed on 21 December 2021)];2010 Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021711s003lbl.pdf.
    1. Bayer HealthCare Pharmaceuticals Magnevist (Gadopentetate Dimeglumine). U.S. Food and Drug Administration. [(accessed on 21 December 2021)];2014 Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019596s057lbl.pdf.

LinkOut - more resources