Elucirem (Gadopiclenol)

What Is Elucirem and What Is It Used For?

Elucirem is the brand name for gadopiclenol, a macrocyclic gadolinium-based contrast agent (GBCA) developed by Guerbet. It was approved by the U.S. Food and Drug Administration (FDA) in September 2022 and by the European Medicines Agency (EMA) in 2023 for use in contrast-enhanced magnetic resonance imaging (MRI). Elucirem represents a significant advancement in the field of MRI contrast agents due to its uniquely high relaxivity properties.

Gadolinium-based contrast agents work by shortening the T1 relaxation time of nearby water protons, which increases signal intensity on T1-weighted MRI sequences. This enhanced signal allows radiologists to better detect and characterize pathological tissues, including tumors, areas of inflammation, vascular abnormalities, and other structural lesions. What distinguishes Elucirem from earlier GBCAs is its relaxivity — approximately twice that of standard agents such as gadobutrol (Gadavist), gadoterate meglumine (Dotarem), or gadoteridol (ProHance).

This high relaxivity means that gadopiclenol can achieve equivalent or superior image enhancement at a dose of 0.05 mmol/kg body weight, compared with the 0.1 mmol/kg typically required for other GBCAs. The practical consequence is that patients receive approximately half the amount of gadolinium, which is clinically relevant given ongoing concerns about gadolinium deposition in the body and potential toxicity in certain patient populations.

Elucirem is indicated for contrast-enhanced MRI of the central nervous system (brain and spine) as well as the rest of the body in adults and children aged 2 years and older. Common clinical scenarios where Elucirem is used include the detection and characterization of brain tumors, spinal lesions, liver masses, musculoskeletal abnormalities, breast pathology, and vascular diseases. It is particularly valuable in oncologic imaging for tumor detection, staging, and monitoring treatment response.

The macrocyclic molecular structure of gadopiclenol is an important safety feature. Macrocyclic chelates encapsulate the gadolinium ion within a cage-like ring structure, providing greater thermodynamic and kinetic stability compared to linear chelates. This stronger binding significantly reduces the likelihood of transmetallation — the process by which gadolinium ions are released from the chelate complex — and consequently lowers the risk of gadolinium tissue deposition and nephrogenic systemic fibrosis (NSF).

What Should You Know Before Receiving Elucirem?

Elucirem is a prescription medication that should only be administered by healthcare professionals experienced in contrast-enhanced MRI procedures. Before receiving this contrast agent, there are several important medical considerations that both patients and clinicians should be aware of. A thorough assessment of the patient's medical history, renal function, and allergy status is essential to ensure safe administration.

Contraindications

Elucirem is contraindicated in patients with known hypersensitivity to gadopiclenol or any of its excipients. Patients who have experienced a previous serious allergic reaction to any gadolinium-based contrast agent should be evaluated carefully, and alternative imaging strategies may need to be considered. While cross-reactivity between different GBCAs is not fully understood, caution is warranted in patients with a history of reactions to other contrast agents.

Warnings and Precautions

Nephrogenic Systemic Fibrosis (NSF): All gadolinium-based contrast agents carry a risk of NSF, a debilitating and potentially fatal condition affecting the skin, joints, and internal organs. NSF has been primarily associated with linear GBCAs in patients with severely impaired kidney function. While the risk with macrocyclic agents like Elucirem is considered very low, it is still not recommended for use in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73m². Renal function should be assessed by measuring serum creatinine and calculating eGFR before administration.

Hypersensitivity Reactions: As with all GBCAs, hypersensitivity reactions including anaphylaxis can occur with Elucirem. These reactions may be mild (such as urticaria, pruritus, or mild nausea), moderate (such as bronchospasm or facial edema), or severe (such as anaphylactic shock). Emergency resuscitation equipment and trained personnel should be immediately available whenever Elucirem is administered. Patients with a history of asthma, allergic disorders, or previous reactions to contrast agents are at increased risk.

Gadolinium Retention: Gadolinium may be retained in the body for months or years after administration of GBCAs. While macrocyclic agents such as gadopiclenol demonstrate significantly lower tissue retention than linear agents, small amounts may still be deposited in various tissues including the brain, bones, skin, and kidneys. The clinical significance of gadolinium retention is an area of active research. The European Medicines Agency (EMA) and American College of Radiology (ACR) recommend using the lowest effective dose and avoiding unnecessary repeated administrations.

Interference with Laboratory Tests: Gadolinium-based contrast agents can interfere with certain laboratory tests, including serum calcium measurements using colorimetric assays. Clinicians should be aware that falsely low serum calcium values may be obtained in the hours following GBCA administration.

Pregnancy and Breastfeeding

There are limited data on the use of Elucirem in pregnant women. Animal studies have shown reproductive toxicity at doses significantly higher than the clinical dose. As a precautionary measure, Elucirem should not be used during pregnancy unless the clinical benefit clearly outweighs the potential risk. The ACR recommends that GBCAs should only be administered to pregnant women when the information is critical to the patient's care and cannot be obtained with non-contrast MRI or other imaging modalities.

It is not known whether gadopiclenol is excreted in human breast milk, although small amounts of other GBCAs have been detected in breast milk. The EMA and ACR guidance suggests that breastfeeding may continue normally after administration of macrocyclic GBCAs, as less than 0.04% of the administered dose is expected to reach the infant through breast milk, and of that, less than 1% is absorbed from the infant's gastrointestinal tract. However, patients who are concerned may choose to interrupt breastfeeding for 24 hours after administration and discard the milk expressed during that period.

Pediatric Use

Elucirem is approved for use in children aged 2 years and older at the same weight-based dose as adults (0.05 mmol/kg body weight). Clinical trials have included pediatric patients and demonstrated comparable safety and efficacy to adults. The safety and efficacy of Elucirem in children under 2 years of age have not been established, and its use in this population is not recommended.

How Does Elucirem Interact with Other Drugs?

Gadopiclenol does not undergo hepatic metabolism and is eliminated almost entirely by renal excretion in an unchanged form. This pharmacokinetic profile means that drug-drug interactions mediated by cytochrome P450 enzymes are not expected. No formal clinical drug interaction studies have identified significant pharmacokinetic interactions with commonly used medications. However, several pharmacological considerations remain important for clinical practice.

Because Elucirem is primarily eliminated by the kidneys, any drug that impairs renal function could theoretically delay its clearance. Nephrotoxic drugs such as aminoglycosides, non-steroidal anti-inflammatory drugs (NSAIDs), certain chemotherapy agents (e.g., cisplatin), and high-dose loop diuretics should be used with caution in patients scheduled to receive Elucirem. Adequate hydration before and after the MRI procedure can help support renal clearance.

Major Interactions

The most clinically significant interaction is the concurrent or closely timed administration of multiple gadolinium-based contrast agents. Using more than one GBCA in a short period increases total gadolinium exposure and may elevate the risk of adverse effects including gadolinium deposition and, in patients with impaired renal function, nephrogenic systemic fibrosis. A reasonable interval of at least 7 days between GBCA administrations is generally recommended when repeat contrast-enhanced MRI studies are required.

Minor Interactions

Interactions with commonly prescribed cardiovascular medications such as ACE inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers are not considered clinically significant. These drugs do not meaningfully alter the pharmacokinetics of gadopiclenol. Patients taking beta-blockers should be noted in the clinical record, as beta-blockade may complicate the management of anaphylactic reactions by making patients less responsive to epinephrine. Alternative agents such as glucagon may be needed in such cases.

What Is the Correct Dosage of Elucirem?

Elucirem is supplied as a clear, colorless to slightly yellow solution for injection at a concentration of 0.5 mmol/mL (equivalent to 0.5 mol/L). It is administered intravenously as a single bolus injection, typically using a power injector at a recommended flow rate of approximately 1–2 mL/second, followed by a saline flush. The dose is calculated based on the patient's body weight.

The key advantage of Elucirem's dosing regimen is that it delivers approximately half the amount of gadolinium compared to standard-dose GBCAs (which typically require 0.1 mmol/kg). This reduced gadolinium exposure is achievable without compromising diagnostic image quality, as demonstrated in multiple Phase III clinical trials comparing gadopiclenol at 0.05 mmol/kg with gadobutrol at 0.1 mmol/kg.

Adults

The recommended dose for adults is 0.05 mmol/kg body weight, equivalent to 0.1 mL/kg of the 0.5 mmol/mL solution. For a 70 kg adult, this equates to approximately 7 mL of Elucirem. The injection is administered as a single intravenous bolus at a rate of 1–2 mL/second, followed by a normal saline flush (typically 20–30 mL). MRI imaging should commence at an appropriate time after injection, depending on the body region and specific imaging protocol being used.

Children

Children aged 2 years and older receive the same weight-based dose as adults: 0.05 mmol/kg body weight. Injection volumes are naturally smaller due to lower body weight. The safety profile in the pediatric population has been evaluated in clinical trials and is consistent with that observed in adults. Elucirem has not been studied in neonates or infants under 2 years of age, and its use in this group is not recommended due to the immature renal function and higher vulnerability of the developing brain.

Elderly

No dose adjustment is required based on age alone. However, elderly patients are more likely to have reduced renal function, and eGFR should be assessed before administration. In patients with moderate renal impairment (eGFR 30–59 mL/min/1.73m²), Elucirem may be used with caution, ensuring adequate hydration before and after the procedure to support renal elimination of the contrast agent.

Missed Dose

Elucirem is administered as a single dose during an MRI procedure and is not used on a scheduled or repeated dosing basis. Therefore, the concept of a missed dose does not apply. If the MRI examination is cancelled or postponed, the dose is simply not given, and a new dose is administered at the time of the rescheduled examination.

Overdose

No cases of clinically significant overdose with Elucirem have been reported in clinical trials. In the event of accidental overdose, the patient should be monitored for signs and symptoms of adverse reactions, particularly renal function impairment. Gadopiclenol can be removed by hemodialysis, although there is no evidence that hemodialysis prevents or treats nephrogenic systemic fibrosis. Supportive care and monitoring of renal function should be provided as clinically indicated.

What Are the Side Effects of Elucirem?

The safety profile of Elucirem has been extensively evaluated in Phase I through Phase III clinical trials involving over 1,700 patients across multiple countries. The overall incidence of adverse events was comparable to or lower than that observed with other approved GBCAs at their standard doses. The reduced gadolinium exposure with Elucirem (half the dose of standard agents) may contribute to a favorable safety profile, although direct comparative safety studies are limited.

Most adverse reactions reported with Elucirem were mild to moderate in severity and resolved spontaneously within hours to days after administration. Below is a frequency-based summary of reported side effects from clinical trials and post-marketing surveillance.

The long-term effects of gadolinium retention in tissues remain an area of active investigation. While macrocyclic agents like Elucirem demonstrate significantly lower tissue deposition compared to linear GBCAs, trace amounts of gadolinium can be detected in various organs after administration. Current evidence does not associate these trace deposits with clinical symptoms in patients with normal renal function, but ongoing surveillance and research continue to evaluate this question.

Patients should report any unexpected symptoms to their healthcare provider after receiving Elucirem. Healthcare professionals are encouraged to report suspected adverse reactions through their national pharmacovigilance system (e.g., the FDA MedWatch program in the United States or the Yellow Card Scheme in the United Kingdom).

How Should You Store Elucirem?

Elucirem is a hospital and clinic-use medication that is stored and handled by healthcare professionals in radiology departments. Patients do not typically need to store this medication at home. However, understanding proper storage conditions is important for healthcare providers to ensure the integrity and efficacy of the product.

The product should be stored at temperatures not exceeding 25°C (77°F). It should be kept in the original packaging to protect from light. Elucirem must not be frozen. If the solution has been frozen, it should be discarded and not used. The vials and pre-filled syringes should be inspected visually before use for particulate matter and discoloration. Elucirem solution should be clear and colorless to slightly yellow; any solution that appears cloudy, contains visible particles, or has changed color should not be used.

Elucirem is provided in single-use vials and pre-filled syringes. Any unused portion remaining in the vial or syringe after administration should be discarded in accordance with local regulations for pharmaceutical waste. The product should not be mixed with other medications in the same syringe or injection line. Once the vial or syringe is opened, the product should be used immediately and not stored for later use.

The shelf life of Elucirem when stored under recommended conditions is typically 3 years from the date of manufacture. Healthcare facilities should follow a first-in, first-out inventory management approach to ensure product freshness. The expiration date printed on the packaging should always be checked before administration.

What Does Elucirem Contain?

The active pharmaceutical ingredient in Elucirem is gadopiclenol, a macrocyclic non-ionic gadolinium chelate complex. Each milliliter of Elucirem solution contains gadopiclenol at a concentration equivalent to 0.5 mmol of gadolinium per milliliter. The molecular weight of gadopiclenol is approximately 752 g/mol, and its chemical structure features a macrocyclic polyamino polycarboxylic acid ligand that forms a highly stable complex with the gadolinium(III) ion.

The macrocyclic structure of gadopiclenol is central to both its efficacy and safety profile. Unlike linear chelates, the macrocyclic cage completely encapsulates the gadolinium ion, providing exceptional thermodynamic stability (log K_therm values significantly higher than linear agents) and kinetic inertness. This means that the gadolinium ion is far less likely to be released from the chelate complex under physiological conditions, a factor that is directly relevant to the reduced risk of gadolinium deposition and nephrogenic systemic fibrosis.

The high relaxivity of gadopiclenol (r1 approximately 12.8 mM−1;s−1 at 1.5 T and 37°C in human plasma) is attributed to its molecular design, which allows two water molecules to simultaneously interact with the gadolinium ion in the inner coordination sphere (a so-called q=2 complex). This is in contrast to most conventional GBCAs, which only accommodate one inner-sphere water molecule (q=1). The dual water coordination dramatically increases the paramagnetic relaxation effect, enabling effective contrast enhancement at lower concentrations.

The excipients (inactive ingredients) in Elucirem include hydrochloric acid and/or sodium hydroxide for pH adjustment to ensure the solution is at physiological pH (approximately 7.0–7.5), and water for injections as the solvent. The solution has an osmolality of approximately 820 mOsmol/kg and a viscosity of approximately 2.1 mPa·s at 37°C, making it suitable for rapid bolus injection through standard intravenous access equipment.

How Does Elucirem Work in the Body?

Magnetic resonance imaging (MRI) relies on the behavior of hydrogen nuclei (protons) in the body when placed in a strong magnetic field. When radiofrequency pulses are applied, these protons absorb energy and become excited. As they return to their equilibrium state, they release energy that is detected by the MRI scanner and converted into images. The rate at which protons return to equilibrium is described by two parameters: T1 (longitudinal) and T2 (transverse) relaxation times.

Gadolinium-based contrast agents like Elucirem shorten the T1 relaxation time of nearby water protons through a process called paramagnetic relaxation enhancement. The gadolinium(III) ion has seven unpaired electrons, making it one of the most powerful paramagnetic ions available for this purpose. When water molecules approach the gadolinium complex and transiently coordinate with the metal center, their protons experience rapid T1 relaxation. On T1-weighted MRI sequences, this results in increased signal intensity (brightness) in tissues where the contrast agent has accumulated.

What makes gadopiclenol exceptional is its molecular design that allows two water molecules to simultaneously occupy the inner coordination sphere of the gadolinium ion (q=2). Most other GBCAs only allow one water molecule (q=1). Additionally, gadopiclenol has been designed with an optimized water exchange rate — the speed at which inner-sphere water molecules are replaced by fresh water molecules from the surrounding environment. The combination of q=2 and optimized water exchange kinetics results in a relaxivity approximately twice that of standard agents, meaning that each molecule of gadopiclenol produces roughly double the signal enhancement compared to an equivalent molecule of, for example, gadobutrol or gadoterate.

After intravenous injection, Elucirem distributes rapidly into the extracellular fluid compartment. It does not cross the intact blood-brain barrier but does enhance lesions where the blood-brain barrier is disrupted (such as most brain tumors, areas of active inflammation, or infection). In the body, it enhances tissues with increased vascularity or altered vascular permeability, which is characteristic of many pathological processes including neoplasms, infections, and inflammatory conditions.

Gadopiclenol is not metabolized in the body and is eliminated almost entirely by renal glomerular filtration. In patients with normal kidney function, the elimination half-life is approximately 1.7 hours, and more than 90% of the administered dose is excreted in the urine within 24 hours. The rapid and complete renal elimination, combined with the high stability of the macrocyclic chelate complex, contributes to the favorable safety profile of Elucirem.