Gadoteric acid, sold under the brand name Dotarem among others, is a macrocycle-structured gadolinium-based MRI contrast agent (GBCA). It consists of the organic acid

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

as a

chelating agent Chelation () is a type of bonding of ions and their 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 l ...

, and

gadolinium Gadolinium is a chemical element; it has Symbol (chemistry), symbol Gd and atomic number 64. It is a silvery-white metal when oxidation is removed. Gadolinium is a malleable and ductile rare-earth element. It reacts with atmospheric oxygen or moi ...

(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 A contrast agent (or contrast medium ...

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, ...

property of gadoteric acid reduces the T1 relaxation 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 generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

, 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 widely used in the United States for Breast MRI imaging for women who have or are suspected to have breast cancer. It is also 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 is also known as the cranium. The cranial cavity is formed by eight cranial bones known as the neurocranium that in human ...

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals. Types There is no de ...

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 regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. 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 cross the intact blood-brain barrier, so it might affect or enhance normal brain tissue in imaging. Dotarem is administered through an intravenous bolus injection, either manually or through a power injection. Dotarem can stay in the body for years.

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'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' 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 – specifical ...

, less so than linears agents. Drugs with gadolinium-based contrasting agents can cause nephrogenic systemic fibrosis (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 aslee ...

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. It was launched on French market in 1989 and was FDA-approved in United States 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, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

MRI. In 2019, GE Healthcare launched gadoteric acid medication (as gadoterate meglumine) under the brand name Clariscan.

Medical uses

Adverse effects

Pharmacology

History

References

Further reading