Optimizing Pediatric MR Imaging with Gadopiclenol

WARNING: RISK ASSOCIATED WITH INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS (NSF)

Risk Associated with Intrathecal Use

Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures.

ELUCIREM is not approved for intrathecal use.

Nephrogenic Systemic Fibrosis

GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of ELUCIREM in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs.

The risk for NSF appears highest among patients with:

Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (for example, age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing.

For patients at highest risk for NSF, do not exceed the recommended ELUCIREM dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration.

Children’s Hospital of Orange County (CHOC) in California performs more than 10,000 MR exams every year, about 74% of which include the administration of a gadolinium-based contrast agent (GBCA). Many of those are scans of the central nervous system (CNS). When Azam Eghbal, MD, medical director of pediatric radiology CHOC, heard about Elucirem™ (gadopiclenol) injection, she was immediately interested in its potential for her pediatric patients.

Elucirem is a high relaxivity, highly stable, macrocyclic GBCA that requires only half the gadolinium dose of conventional, nonspecific GBCAs.1,2,4 These characteristics make it ideal for pediatric populations (age 2 years and older), especially those who require frequent MR contrast scans.

“We’re using half a dose of contrast compared to other GBCAs. Instead of using 0.1 millimoles per kilogram, we are using of 0.05 millimoles per kilogram, which means we’re giving 50% less contrast,” said Dr Eghbal.

Balancing image quality with safety

CHOC implemented Elucirem in October 2023 for all MR brain scans, primarily due to its macrocyclic structure, which contributes to its kinetic stability and safety profile.3,4

The administration of a GBCA improves the contrast between lesions and surrounding tissues by accelerating the relaxation of protons through interaction with gadolinium atoms.3 Elucirem delivers twice as much interaction as other GBCAs, resulting in the highest relaxivity among nonspecific GBCAs.3

This high T1 relaxivity, was another factor in adding Elucirem to CHOC’s formulary. “Everything is bright, whether it’s a contrast-enhancing tumor, pathology or normal structures, from the vessels and arterial and venous systems to the normal nasal mucosa and extraocular muscles of the orbits,” she said.

The combination of the safety profile, high T1 relaxivity and high kinetic stability gives Dr Eghbal more confidence to accurately diagnose abnormalities. “For vulnerable patients, the impact of Elucirem is tremendous. It’s a victory for us and a victory for our pediatric patients,” states Eghbal.

The clinical utility of Elucirem in pediatric MR imaging (age 2 years and older)

In a video case study titled Contrast Enhanced Pediatric MRI, Dr Eghbal presented several cases showing how CHOC is preserving high image quality while reducing the amount of gadolinium administered to its pediatric patients.

In one case, a 4-year-old patient presented with symptoms of encephalitis. Axial T2 FLAIR images showed extensive bilateral areas of abnormal signal intensity throughout the brain. This indicated infratentorial and supratentorial events, as well as contents in the right lateral ventricle within the midbrain.

T1 axial post-contrast images were captured using only 2 millimoles of Elucirem, half the 4 millimole dose of other conventional GBCAs. “You can see the enhancement of this contrast in areas of both pathology and normal structures. From regular vessels to venous sinuses, all vessels are enhancing well. There is no question about the properties of this contrast when it comes to its utility for the pediatric patients,” she said.

In another case, a 2-year-old returned for a post-surgical follow-up after a pilocytic astrocytoma brain tumor dissection. T1 axial post-contrast images taken a year prior showed residual enhancement at the surgical bed. In comparison, new images taken with Elucirem showed comparable enhancement in that region, including enhancement of normal structures, such as extraocular muscles or nasal mucosa.

“Elucirem delivers equal T1 relaxivity and enhancement at half a dose of the contrast,” she said.

In another case, a 15-year-old with an orbital pseudotumor who frequently received MR imaging at the hospital presented with a headache. In 2022, the patient received 11 mls of another conventional GBCA that resulted in images showing no pathologic findings. On a repeat scan using 5.6mls of Elucirem, the images showed vessel enhancement and eliminated the need to perform an MRA or MRV to rule out other pathologies. “I can see the vessels so perfectly with Elucirem that I have no doubt there's no thrombosis, vasculitis, stenosis or other wall pathology that would require further imaging, which would add scan time, contrast and cost,” she said.

View these pediatric MRI video case studies

Expanding the use of gadopiclenol

Dr Eghbal plans to expand the use of Elucirem to all other areas of MR imaging where Elucirem is indicated, which will have an even greater impact on more patients. “Elucirem can help pediatric patients who might have hundreds of MRs throughout their lifetimes, and we can reduce the gadolinium dose.”

References

1. Loevner LA, Kolumban B, Hutóczki G, et al. Efficacy and safety of gadopiclenol for contrast-enhanced MRI of the central nervous system: the PICTURE randomized clinical trial. Invest Radiol. 2023;58(5):307-313. doi:10.1097/RLI.0000000000000944
2. Kuhl C, Csőszi T, Piskorski W, Miszalski T, Lee JM, Otto PM. Efficacy and Safety of Half-Dose Gadopiclenol versus Full-Dose Gadobutrol for Contrast-enhanced Body MRI. Radiology. 2023;308(1):e222612. doi:10.1148/radiol.222612
3. Robic C, Port M, Rousseaux O, et al. Physicochemical and pharmacokinetic profiles of gadopiclenol: a new macrocyclic gadolinium chelate with high T1 relaxivity. Invest Radiol. 2019;54(8):475-484. doi:10.1097/RLI.0000000000000563 
4. Elucirem Package insert. Guerbet LLC; 2024.

ELUCIREM™ (gadopiclenol) injection Important Safety Information

Indications and Usage

ELUCIREM^TM (gadopiclenol) injection is indicated in adult and pediatric patients aged 2 years and older for use with magnetic resonance imaging (MRI) to detect and visualize lesions with abnormal vascularity in the central nervous system (brain, spine, and associated tissues), and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system).

Contraindications

Contraindicated in patients with history of hypersensitivity reactions to ELUCIREM.

Warnings and Precautions

• Risk Associated with Intrathecal Use: Intrathecal administration of GBCAs can cause serious adverse reactions including death, coma, encephalopathy, and seizures. The safety and effectiveness of ELUCIREM have not been established with intrathecal use. ELUCIREM is not approved for intrathecal use.
• Nephrogenic Systemic Fibrosis: GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of ELUCIREM among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities.
• Hypersensitivity Reactions: With GBCAs, serious hypersensitivity reactions have occurred. Before ELUCIREM administration, assess all patients for any history of a reaction to contrast media, bronchial asthma and/or allergic disorders. These patients may have an increased risk for a hypersensitivity reaction to ELUCIREM.
• Gadolinium Retention: Gadolinium is retained for months or years in several organs. The highest concentrations have been identified in the bone, followed by other organs (e.g. brain, skin, kidney, liver, and spleen). While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions. Minimize repetitive GBCA imaging studies, particularly closely spaced studies when possible.
• Acute Kidney Injury: In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. The risk of acute kidney injury may increase with increasing dose of the contrast agent.
• Extravasation and Injection Site Reactions: Injection site reactions such as injection site pain have been reported in the clinical studies with ELUCIREM. Extravasation during ELUCIREM administration may result in tissue irritation. Ensure catheter and venous patency before the injection of ELUCIREM.
• Interference with Visualization of Lesions Visible with Non-Contrast MRI: As with any GBCA, ELUCIREM may impair the visualization of lesions seen on non-contrast MRI.

Adverse Reactions:

In clinical trials, the most frequent adverse reactions that occurred in > 0.2% of patients who received ELUCIREM included: injection site pain, headache, nausea, injection site warmth, injection site coldness, dizziness, and localized swelling.

Postmarketing Experience: Acute pancreatitis with onset within 48 hours after GBCA administration.

Use in Specific Populations

• Pregnancy: GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. There are no available data on ELUCIREM use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
• Lactation: There are no data on the presence of ELUCIREM in human milk, the effects on the breastfed infant, or the effects on milk production. However, published lactation data on other GBCAs indicate that 0.01 to 0.04% of the maternal gadolinium dose is excreted in breast milk.
• Pediatric Use: The safety and effectiveness of ELUCIREM have not been established in pediatric patients younger than 2 years of age.
• Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.
• Renal Impairment: In patients with renal impairment, the exposure of gadopiclenol is increased compared to patients with normal renal function. This may increase the risk of adverse reactions such as NSF. No dose adjustment of ELUCIREM is recommended for patients with renal impairment.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see the full Prescribing Information, including the Medication Guide, for additional important safety information.

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