Gadoteric acid

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Gadoteric acid
Gadoteric acid.png
Clinical data
Trade names Artirem, Dotarem, Clariscan, others [1]
Other namesDOTA-Gd, Gadoterate meglumine (USAN US)
AHFS/Drugs.com International Drug Names
License data
Routes of
administration 		Intravenous
ATC code
Legal status
Legal status
Identifiers
  • gadolinium(3+) 2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C16H25GdN4O8
Molar mass 558.65 g·mol−1
3D model (JSmol)
  • [Gd+3].OC(=O)CN1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1
  • InChI=1S/C16H28N4O8.Gd/c21-13(22)9-17-1-2-18(10-14(23)24)5-6-20(12-16(27)28)8-7-19(4-3-17)11-15(25)26;/h1-12H2,(H,21,22)(H,23,24)(H,25,26)(H,27,28);/q;+3/p-3
  • Key:GFSTXYOTEVLASN-UHFFFAOYSA-K
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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 as a chelating agent, and gadolinium (Gd3+), and is used in form of the meglumine salt (gadoterate meglumine). [3] [4] The paramagnetic property of gadoteric acid reduces the T1 relaxation time (and to some extent the T2 and T2* relaxation times) in MRI, 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. [6]

Contents

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 lesions with abnormal vascularity or abnormalities in the blood–brain barrier. 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. [6] Dotarem is administered through an intravenous bolus injection, either manually or through a power injection. Dotarem can stay in the body for years. [3] [4]

Adverse effects

It is retained in the brain at a measurable level after an injection at standard dose (0.1 mmol/kg). [7] In vitro studies found it neurotoxic, less so than linears agents. [8]

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. [3] [4] [9]

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. [10]

Pharmacology

A 2020 study found Clariscan was retained more in the cerebrum, cerebellum, kidney and liver of rats than those injected with Dotarem. [11]

History

The drug, under the brand name Dotarem, was brought to market by Guerbet. [12] It was launched on French market in 1989 and was FDA-approved in United States in March 2013. [12] As of 2013, gadoteric acid was approved in around 70 countries. [13] [14] Dotarem is the seventh FDA-approved GBCA for use in central nervous system MRI.[ citation needed ]

In 2019, GE Healthcare launched gadoteric acid medication (as gadoterate meglumine) under the brand name Clariscan. [4] [15]

Related Research Articles

<span class="mw-page-title-main">Gadolinium</span> Chemical element, symbol Gd and atomic number 64

Gadolinium is a chemical element; it has symbol Gd and atomic number 64. Gadolinium is a silvery-white metal when oxidation is removed. It is a malleable and ductile rare-earth element. Gadolinium reacts with atmospheric oxygen or moisture slowly to form a black coating. Gadolinium below its Curie point of 20 °C (68 °F) is ferromagnetic, with an attraction to a magnetic field higher than that of nickel. Above this temperature it is the most paramagnetic element. It is found in nature only in an oxidized form. When separated, it usually has impurities of the other rare-earths because of their similar chemical properties.

<span class="mw-page-title-main">Magnetic resonance imaging</span> Medical imaging technique

Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves to generate images of the organs in the body. MRI does not involve X-rays or the use of ionizing radiation, which distinguishes it from computed tomography (CT) and positron emission tomography (PET) scans. MRI is a medical application of nuclear magnetic resonance (NMR) which can also be used for imaging in other NMR applications, such as NMR spectroscopy.

<span class="mw-page-title-main">Arthrogram</span>

An arthrogram is a series of images of a joint after injection of a contrast medium, usually done by fluoroscopy or MRI. The injection is normally done under a local anesthetic such as Novocain or lidocaine. The radiologist or radiographer performs the study using fluoroscopy or x-ray to guide the placement of the needle into the joint and then injects around 10 ml of contrast based on age. There is some burning pain from the anesthetic and a painful bubbling feeling in the joint after the contrast is injected. This only lasts 20 – 30 hours until the Contrast is absorbed. During this time, while it is allowed, it is painful to use the limb for around 10 hours. After that the radiologist can more clearly see what is going on under your skin and can get results out within 24 to 48 hours.

<span class="mw-page-title-main">Diatrizoate</span> Chemical compound

Diatrizoate, also known as amidotrizoate, Gastrografin, is a contrast agent used during X-ray imaging. This includes visualizing veins, the urinary system, spleen, and joints, as well as computer tomography. It is given by mouth, injection into a vein, injection into the bladder, through a nasogastric tube, or rectally.

<span class="mw-page-title-main">Magnetic resonance angiography</span> Group of techniques based on magnetic resonance imaging (MRI) to image blood vessels.

Magnetic resonance angiography (MRA) is a group of techniques based on magnetic resonance imaging (MRI) to image blood vessels. Magnetic resonance angiography is used to generate images of arteries in order to evaluate them for stenosis, occlusions, aneurysms or other abnormalities. MRA is often used to evaluate the arteries of the neck and brain, the thoracic and abdominal aorta, the renal arteries, and the legs.

A contrast agent is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radiopharmaceuticals, which emit radiation themselves. In x-ray imaging, contrast agents enhance the radiodensity in a target tissue or structure. In magnetic resonance imaging, contrast agents shorten the relaxation times of nuclei within body tissues in order to alter the contrast in the image.

<span class="mw-page-title-main">Gadopentetic acid</span> Complex of gadolinium by DTPA

Gadopentetic acid, sold under the brand name Magnevist, is a gadolinium-based MRI contrast agent.

Magnetic resonance elastography (MRE) is a form of elastography that specifically leverages MRI to quantify and subsequently map the mechanical properties of soft tissue. First developed and described at Mayo Clinic by Muthupillai et al. in 1995, MRE has emerged as a powerful, non-invasive diagnostic tool, namely as an alternative to biopsy and serum tests for staging liver fibrosis.

<span class="mw-page-title-main">Gadodiamide</span> Chemical compound

Gadodiamide, sold under the brand name Omniscan, is a gadolinium-based MRI contrast agent (GBCA), used in magnetic resonance imaging (MRI) procedures to assist in the visualization of blood vessels.

Nephrogenic systemic fibrosis is a rare syndrome that involves fibrosis of the 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. Epidemiological studies suggest that the incidence of NSF is unrelated to gender or ethnicity and it is not thought to have a genetic basis. After GBCAs were identified as a cause of the disorder in 2006, and screening and prevention measures put in place, it is now considered rare.

MRI contrast agents are contrast agents used to improve the visibility of internal body structures in magnetic resonance imaging (MRI). The most commonly used compounds for contrast enhancement are gadolinium-based contrast agents (GBCAs). Such MRI contrast agents shorten the relaxation times of nuclei within body tissues following oral or intravenous administration.

<span class="mw-page-title-main">Gadobutrol</span> Chemical compound

Gadobutrol (INN) (Gd-DO3A-butrol) is a gadolinium-based MRI contrast agent (GBCA).

<span class="mw-page-title-main">Iobitridol</span> Pharmaceutical drug

Iobitridol is a pharmaceutical drug used as an iodine-based radiocontrast agent in X-ray imaging. It is injected into blood vessels, joints, or body cavities such as the uterus, and filtered out by the kidneys. Its most common adverse effect is nausea. Severe allergic reactions are rare.

<span class="mw-page-title-main">Ioxaglic acid</span> Chemical compound

Ioxaglic acid is pharmaceutical drug used as an iodinated contrast medium for X-ray imaging. It has low osmolality, typically resulting in fewer side effects than high-osmolality media. It is manufactured by Guerbet, but marketing in the US has been discontinued. As of 2021, it may still be available in some European countries.

<span class="mw-page-title-main">Gadobenic acid</span> Complex of gadolinium by a chelating agent derived from DTPA

Gadobenic acid is a complex of gadolinium with the ligand BOPTA. In the form of the methylglucamine salt meglumine gadobenate (INNm) or gadobenate dimeglumine (USAN), it is used as a gadolinium-based MRI contrast medium.

<span class="mw-page-title-main">Val Murray Runge</span> American professor of radiology

Val Murray Runge is an American and Swiss professor of radiology and the editor-in-chief of Investigative Radiology. Runge was one of the early researchers to investigate the use of gadolinium-based contrast agents for magnetic resonance imaging (MRI), giving the first presentation in this field, followed two years later by the first presentation of efficacy. His research also pioneered many early innovations in MRI, including the use of tilted planes and respiratory gating. His publication on multiple sclerosis in 1984 represented the third and largest clinical series investigating the role of MRI in this disease, and the first to show characteristic abnormalities on MRI in patients whose CT was negative.

<span class="mw-page-title-main">Perfusion MRI</span>

Perfusion MRI or perfusion-weighted imaging (PWI) is perfusion scanning by the use of a particular MRI sequence. The acquired data are then post-processed to obtain perfusion maps with different parameters, such as BV, BF, MTT and TTP.

<span class="mw-page-title-main">Sodium thiosulfate (medical use)</span>

Sodium thiosulfate, also spelled sodium thiosulphate, is used as a medication to treat cyanide poisoning, pityriasis versicolor, and to decrease side effects from cisplatin. For cyanide poisoning, it is often used after the medication sodium nitrite and is typically only recommended for severe cases. It is either given by injection into a vein or applied to the skin.

A central nervous system tumor is an abnormal growth of cells from the tissues of the brain or spinal cord. CNS tumor is a generic term encompassing over 120 distinct tumor types. Common symptoms of CNS tumors include vomiting, headache, changes in vision, nausea, and seizures. A CNS tumor can be detected and classified via neurological examination, medical imaging, such as x-ray imaging, magnetic resonance imaging (MRI) or computed tomography (CT), or after analysis of a biopsy.

<span class="mw-page-title-main">Gadopiclenol</span> MRI contrast agent

Gadopiclenol, sold under the brand name Elucirem among others, is a contrast agent used with magnetic resonance imaging (MRI) to detect and visualize lesions with abnormal vascularity in the central nervous system and in the body. Gadopiclenol is a paramagnetic macrocyclic non-ionic complex of gadolinium.

References

  1. ↑ "Gadoteric Acid International". Drugs.com. 6 January 2021. Retrieved 21 January 2021.
  2. ↑ "Dotagraf 0.5 mmol/ml solution for injection - Summary of Product Characteristics (SmPC)". (emc). Retrieved 29 August 2021.
  3. 1 2 3 4 "Dotarem- gadoterate meglumine injection". DailyMed. Retrieved 29 August 2021.
  4. 1 2 3 4 5 "Clariscan- gadoterate meglumine injection, solution". DailyMed. Retrieved 29 August 2021.
  5. ↑ "Gadoteric acid intra articular formulation list nationally authorised medicinal products" (PDF). ema.europa.eu. Retrieved 20 May 2023.
  6. 1 2 DrugBank, ed. (22 August 2016). "Gadoteric acid". DrugBank.
  7. ↑ Stanescu AL, Shaw DW, Murata N, Murata K, Rutledge JC, Maloney E, et al. (March 2020). "Brain tissue gadolinium retention in pediatric patients after contrast-enhanced magnetic resonance exams: pathological confirmation". Pediatric Radiology. 50 (3): 388–396. doi:10.1007/s00247-019-04535-w. PMID   31989188. S2CID   210913930.
  8. ↑ Bower DV, Richter JK, von Tengg-Kobligk H, Heverhagen JT, Runge VM (August 2019). "Gadolinium-Based MRI Contrast Agents Induce Mitochondrial Toxicity and Cell Death in Human Neurons, and Toxicity Increases With Reduced Kinetic Stability of the Agent". Investigative Radiology. 54 (8): 453–463. doi:10.1097/RLI.0000000000000567. PMID   31265439. S2CID   164486744.
  9. ↑ Todd DJ, Kay J (2016). "Gadolinium-Induced Fibrosis". Annual Review of Medicine. 67: 273–91. doi:10.1146/annurev-med-063014-124936. PMID   26768242.
  10. ↑ "Summary of product characteristics - Dotarem 279.32 mg/ml Solution for injection in pre-filled syringes" (PDF). Guerbet. Archived from the original (PDF) on 13 December 2022. Retrieved 13 December 2022.
  11. ↑ Bussi S, Coppo A, Celeste R, Fanizzi A, Fringuello Mingo A, Ferraris A, et al. (February 2020). "Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats". Insights into Imaging. 11 (1): 11. doi: 10.1186/s13244-019-0824-5 . PMC   7000570 . PMID   32020385.
  12. 1 2 Hollmer M (6 January 2014). "Dotarem: A safe(r) gadolinium-based contrast imaging agent". FierceBiotech.
  13. ↑ "Gadoteric Acid international brands". Drugs.com. Retrieved 7 March 2017.
  14. ↑ Guerbet LLC (14 February 2013). "Advisory Committee Briefing Document for NDA 204-781". FDA.
  15. ↑ "Clariscan 0.5 mmol/ ml solution for injection" (PDF). Archived from the original (PDF) on 1 March 2017. Retrieved 28 February 2017.

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