Gadoteric acid, sold under the brand name Dotarem among others, is a

macrocycle Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry. ...

-structured gadolinium-based MRI contrast agent (GBCA). It consists of the organic acid

DOTA ''Dota'' is a series of strategy video games by Valve. The series began in 2003 with the release of ''Defense of the Ancients'' (''DotA''), a fan-developed multiplayer online battle arena (MOBA) mod for the video game '' Warcraft III: Reign of ...

as a

chelating agent Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands are ...

, and

gadolinium Gadolinium is a chemical element with the symbol Gd and atomic number 64. Gadolinium is a silvery-white metal when oxidation is removed. It is only slightly malleable and is a ductile rare-earth element. Gadolinium reacts with atmospheric oxygen ...

(Gd³⁺), and is used in form of the

meglumine Meglumine is a sugar alcohol derived from glucose that contains an amino group modification. It is often used as an excipient in pharmaceuticals and in conjunction with iodinated compounds in contrast media such as diatrizoate meglumine, ioth ...

salt (gadoterate meglumine). The

paramagnetic Paramagnetism is a form of magnetism whereby some materials are weakly attracted by an externally applied magnetic field, and form internal, induced magnetic fields in the direction of the applied magnetic field. In contrast with this behavior, d ...

property of gadoteric acid reduces the T1

relaxation time In the physical sciences, relaxation usually means the return of a perturbed system into equilibrium. Each relaxation process can be categorized by a relaxation time τ. The simplest theoretical description of relaxation as function of time ' ...

(and to some extent the T2 and T2* relaxation times) in

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

, which is the source of its clinical utility. Because it has magnetic properties, gadoteric acid develops a magnetic moment when put under a magnetic field, which increases the signal intensity (brightness) of tissues during MRI imaging.

Medical uses

It is used for imaging of blood vessels and inflamed or diseased tissue where the blood vessels become 'leaky'. It is often used when viewing

intracranial The cranial cavity, also known as intracranial space, is the space within the skull that accommodates the brain. The skull minus the mandible is called the ''cranium''. The cavity is formed by eight cranial bones known as the neurocranium that in ...

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

s with abnormal

vascularity Vascularity, in bodybuilding, is the condition of having many highly visible, prominent, and often extensively-ramified superficial veins. The skin appears "thin"—sometimes virtually transparent—due to an extreme reduction of subcutaneous fat ...

or abnormalities in the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...

. Gadoteric acid is used for MRI imaging of the brain, spine, and associated tissues for adult and pediatric (2 years of age or older) patients. The meglumine salt it takes the form of crosses the blood brain barrier of tissue with abnormal vasculature, highlighting the affected area with MRI. Gadoterate does not cross the intact blood-brain barrier, so it does not affect or enhance normal brain tissue in imaging. Dotarem is administered through an intravenous bolus injection, either manually or through a power injection.

Adverse effects

It is retained in the brain at a measurable level after an injection at standard dose (0.1 mmol/kg). ''

In vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' studies found it

neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...

, less so than linears agents. Drugs with gadolinium-based contrasting agents can cause

nephrogenic systemic fibrosis Nephrogenic systemic fibrosis is a rare syndrome that involves fibrosis of skin, joints, eyes, and internal organs. NSF is caused by exposure to gadolinium in gadolinium-based MRI contrast agents (GBCAs) in patients with impaired kidney function. ...

(NSF, or gadolinium-induced fibrosis) for those with impaired elimination of the drug. Those most at risk for NSF include patients with chronic or severe kidney disease and acute kidney injury. The rate of side effects are uncommon (0.1 to 1.0%), including nausea, headache, injection site reactions, hypertension, hypotension, dizziness, feeling hot, and

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

Pharmacology

A 2020 study found Clariscan was retained more in the cerebrum, cerebellum, kidney and liver of rats than those injected with Dotarem.

History

The drug, under the brand name Dotarem, was brought to market by

Guerbet Guerbet () is a France-based manufacturer of contrast agents used in medical imaging. The company was founded in 1926 by André Guerbet, the son of Marcel Guerbet who in 1901 discovered Lipiodol – the first Iodinated contrast, iodinated X-ray con ...

. It was launched on

French French (french: français(e), link=no) may refer to: * Something of, from, or related to France ** French language, which originated in France, and its various dialects and accents ** French people, a nation and ethnic group identified with Franc ...

market in 1989 and was

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

-approved in

USA The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

in March 2013. As of 2013, gadoteric acid was approved in around 70 countries. Dotarem is the seventh FDA-approved GBCA for use in

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

MRI. In 2019,

GE Healthcare GE HealthCare is a subsidiary of American multinational conglomerate General Electric incorporated in New York and headquartered in Chicago, Illinois. As of 2017, it is a manufacturer and distributor of diagnostic imaging agents and radiopharma ...

launched gadoteric acid medication (as gadoterate meglumine) under the brand name Clariscan.

References

External links