Gadoteric acid explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:407376289
Usan:Gadoterate meglumine
Tradename:Artirem, Dotarem, Clariscan, others[1]
Dailymedid:Gadoterate meglumine
Routes Of Administration:Intravenous
Atc Prefix:V08
Atc Suffix:CA02
Legal Ca:Rx-only
Legal Ca Comment:[2]
Legal Uk:POM
Legal Uk Comment:[3]
Legal Us:Rx-only
Legal Us Comment:[4] [5]
Legal Eu:Rx-only
Legal Eu Comment:[6]
Legal Status:Rx-only
Cas Number:72573-82-1
Pubchem:158536
Drugbank:DB09132
Chemspiderid:139460
Unii:QVF9Y6955W
Kegg:D08007
Chebi:73732
Chembl:3833326
Synonyms:DOTA-Gd
Iupac Name:gadolinium(3+) 2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate
C:16
H:25
Gd:1
N:4
O:8
Smiles:[Gd+3].OC(=O)CN1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1
Stdinchi: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
Stdinchikey:GFSTXYOTEVLASN-UHFFFAOYSA-K

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).[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.

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.[7] Dotarem is administered through an intravenous bolus injection, either manually or through a power injection. Dotarem can stay in the body for years. [5]

Adverse effects

It is retained in the brain at a measurable level after an injection at standard dose (0.1 mmol/kg).[8] In vitro studies found it neurotoxic, less so than linears agents.[9]

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.[10]

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.[11]

Pharmacology

A 2020 study found Clariscan was retained more in the cerebrum, cerebellum, kidney and liver of rats than those injected with Dotarem.[12]

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.[13] As of 2013, gadoteric acid was approved in around 70 countries.[14] [15] Dotarem is the seventh FDA-approved GBCA for use in central nervous system MRI.

In 2019, GE Healthcare launched gadoteric acid medication (as gadoterate meglumine) under the brand name Clariscan.[16]

Further reading

Notes and References

  1. Web site: Gadoteric Acid International . Drugs.com . 6 January 2021 . 21 January 2021.
  2. Web site: Health Canada New Drug Authorizations: 2016 Highlights . . 14 March 2017 . 7 April 2024.
  3. Web site: Dotagraf 0.5 mmol/ml solution for injection - Summary of Product Characteristics (SmPC) . (emc) . 29 August 2021.
  4. Web site: Dotarem- gadoterate meglumine injection . DailyMed . 29 August 2021.
  5. Web site: Clariscan- gadoterate meglumine injection, solution . DailyMed . 29 August 2021.
  6. Web site: Gadoteric acid intra articular formulation list nationally authorised medicinal products. ema.europa.eu. 20 May 2023.
  7. Web site: 22 August 2016. Gadoteric acid. DrugBank.
  8. Brain tissue gadolinium retention in pediatric patients after contrast-enhanced magnetic resonance exams: pathological confirmation . Stanescu AL, Shaw DW, Murata N, Murata K, Rutledge JC, Maloney E, Maravilla KR . 50 . Pediatric Radiology . 3 . March 2020 . 31989188 . 10.1007/s00247-019-04535-w . 388–396 . 210913930.
  9. Gadolinium-Based MRI Contrast Agents Induce Mitochondrial Toxicity and Cell Death in Human Neurons, and Toxicity Increases With Reduced Kinetic Stability of the Agent . Bower DV, Richter JK, von Tengg-Kobligk H, Heverhagen JT, Runge VM . 54 . Investigative Radiology . 8 . August 2019 . 31265439 . 10.1097/RLI.0000000000000567 . 453–463 . 164486744.
  10. Todd DJ, Kay J . 2016 . Gadolinium-Induced Fibrosis . Annual Review of Medicine . 67 . 273–91 . 10.1146/annurev-med-063014-124936 . 26768242.
  11. Web site: Summary of product characteristics - Dotarem 279.32 mg/ml Solution for injection in pre-filled syringes . Guerbet . 13 December 2022 . https://web.archive.org/web/20221213123921/https://www.guerbet.com/media/khnpqyfu/spc-dotarem-pfs_dec-2020.pdf . 13 December 2022.
  12. Bussi S, Coppo A, Celeste R, Fanizzi A, Fringuello Mingo A, Ferraris A, Botteron C, Kirchin MA, Tedoldi F, Maisano F . February 2020 . Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats . Insights into Imaging . 11 . 1 . 11 . 10.1186/s13244-019-0824-5 . 7000570 . 32020385 . free .
  13. News: Hollmer M . Dotarem: A safe(r) gadolinium-based contrast imaging agent. FierceBiotech. 6 January 2014.
  14. Web site: Gadoteric Acid international brands . Drugs.com. 7 March 2017.
  15. Web site: Guerbet LLC. Advisory Committee Briefing Document for NDA 204-781. https://web.archive.org/web/20170307130911/https://www.fda.gov/downloads/AdvisoryCommittees/UCM339378 . 7 March 2017 . FDA. 14 February 2013.
  16. Web site: Clariscan 0.5 mmol/ ml solution for injection . 28 February 2017 . https://web.archive.org/web/20170301092722/http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1487912585095.pdf . 1 March 2017 . dead.