1887

Radiographic contrast agents

See BSAVA Guide to Procedures in Small Animal Practice

Several gadolinium chelates are used for magnetic resonance imaging (MRI) contrast studies. None of them is authorized for veterinary use and all are POM.

Gadolinium is a paramagnetic agent and exerts its effects due to seven unpaired electrons, which cause a shortening of T1 and T2 relaxation times of adjacent tissues. This results in increased signal intensity on T1-weighted MR images. Unbound gadolinium is highly toxic and so is chelated to reduce toxicity. Gadolinium chelates do not cross the normal blood–brain barrier due to their large molecular size.

  • During MRI examination to identify areas of abnormal vascularization or increased interstitial fluid, delineate masses and demonstrate disruption of the blood–brain barrier and areas of inflammation.
  • Gadodiamide, gadobutrol, gadoteric acid and gadobenic acid are also used for contrast-enhanced magnetic resonance angiography (MRA).
  • The low concentration form of gadopentetic acid (2 mmol/l) is authorized for intra-articular use for MR arthrography in humans.
  • Gadobenic acid and gadoxetic acid are also transported across hepatocyte cell membranes (gadoxetic acid via organic anionic-acid transporting peptide 1) and are used in the characterization of liver lesions.

Contact with skin and eyes may cause mild irritation.

Use with caution in cardiac disease, pre-existing renal disease and neonates. Contraindicated in severe renal impairment.

Nephrogenic systemic fibrosis (most commonly associated with gadodiamide but also gadopentetic acid and gadoversetamide) reported in humans but not in animals. Increase in QT interval and other arrhythmias have also been reported, and cardiac monitoring is recommended in the event of accidental overdosage. Transient episodes of shortness of breath following intravenous administration of gadoxetic acid have been reported in humans. Many contrast agents are hyper-osmolar and irritant if extravasation occurs (although studies in animals have shown gadopentetic acid and gadoteridol to be less toxic to subcutaneous tissues than an equal volume of iodinated contrast media), and therefore should be given through an intravenous catheter. Anaphylaxis occurs rarely (0.001% - 0.01% in human studies). May cause a transient increase in serum bilirubin if there is pre-existing hepatic disease. Retained gadolinium deposits in certain areas of the brain have been reported recently in human patients, the clinical significance of these deposits is unknown at present. May cause fetal abnormalities in rabbits.

May have interactions with Class 1a and 3 antiarrhythmics. Gadobenic acid may compete for cannalicular multispecific organic anionic transporter sites. Caution should be used if administering anthracyclines, vinca alkyloids and other drugs using this transporter. Anionic drugs excreted in bile (e.g. rifampicin) may reduce hepatic uptake of gadoxetic acid, reducing contrast enhancement. May affect some laboratory results, e.g. serum iron determination using complexometric methods, transient increase in liver enzymes, some linear non-ionic gadolinium-based contrast media (gadodiamide, gadoversetamide) may cause false reduction in serum calcium measurement.

Should be used routinely for MRI examinations of the brain. Use for MRI of other body regions if abnormal vascularization, inflammation or neoplasia is suspected, for postsurgical evaluation or if MRI study is normal despite significant clinical signs. Post-contrast images should ideally be obtained within 30 minutes of contrast administration. Total doses should not exceed 0.3 mmol/kg (varies with product).

0.1 mmol/kg i.v. (all except gadoxetic acid). Give as bolus if performing MRA, dynamic contrast or liver studies; 0.025 mmol/kg i.v. bolus of gadoxetic acid for liver studies; 0.05 mmol/kg of gadobenic acid for liver studies. Repeat doses (not gadoxetic acid) of up to 0.3 mmol/kg total dose may be helpful in some cases if poor contrast enhancement with standard dose or for detection of metastases and if using low-field scanner. Enhancement visible up to 45–60 minutes post-administration.  

Generic name

Trade name

Manufacturer

Authorized indications in humans

Excretion

Properties

Protein binding

Dose

Formulations

Gadopentetic acid

Magnevist

Bayer

CNS; whole body (excluding heart); arthrography

Renal

Linear Ionic 1960 mOsm/kg

0

0.1–0.3 mmol/kg

469 mg/ml, 2 mmol/l

5, 10, 15, 20 ml vials; 10, 15, 20 ml pre-filled syringes; 50, 100 ml pharmacy bulk package

Gadoteric acid

Dotarem

Guerbet Laboratories Ltd

CNS; whole body; MRA

Renal

Cyclic Ionic 1350 mOsm/kg

0

0.1–0.3 mmol/kg

279.3 mg/ml

5, 10, 15, 20 ml vials; 15, 20 ml pre-filled syringes

Gadoteridol

Prohance

Bracco

CNS; whole body

Renal

Cyclic Non-ionic 630 mOsm/kg

0

0.1 mmol/kg

279.3 mg/ml

5, 10, 15, 20 ml vials; 5, 10, 15, 17 ml pre-filled syringes

Gadodiamide

Omniscan

Nycomed Amersham

CNS; whole body

Renal

Linear Non-ionic 789 mOsm/kg

0

0.1–0.3 mmol/kg

287 mg/ml

5, 10, 15, 20, 40, 50 ml vials; 10, 15, 20 ml pre-filled syringes

Gadobutrol

Gadovist

Bayer

CNS

Renal

Cyclic Non-ionic 1603 mOsm/kg

0

0.1 mmol/kg

604.72 mg/ml

7.5, 10, 15 ml vials; 7.5, 10, 15 ml pre-filled syringes; 30, 65 ml bulk packages

Gadoxetic acid

Primovist

Bayer

Liver

50% renal, 50% biliary

Linear Ionic 688 mOsm/kg

<15%

0.025 mmol/kg

181.43 mg/ml

10 ml pre-filled syringes

Gadobenic acid

MultiHance

Bracco

CNS; liver; MRA; breast

Renal (biliary up to 4%)

Linear Ionic 1970 mOsm/kg

<5%

CNS: 0.1 mmol/kg; liver: 0.05 mmol/kg

334 mg/ml

5, 10, 15, 20 ml vials

Gadoversetamide

Optimark

Covidien

CNS; liver

Renal

Linear Non-ionic 1110 mOsm/kg

0

0.1 mmol/kg

330 mg/ml

10, 15, 20, 30 ml pre-filled syringes

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