Gadopiclenol Shows Promise for MR Lymphangiography
First-in-human experience suggests potential for strong signal with lower gadolinium dose
Gadopiclenol, a newer-generation gadolinium-based contrast agent (GBCA), demonstrated safety and produced diagnostic-quality images in a first-in-human experience involving nodal and dermal injection for dynamic contrast-enhanced MR lymphangiography (DCE-MRL).
Findings from a recent study published in Radiology: Cardiothoracic Imaging study suggest that the agent may provide a strong signal using a lower gadolinium dose, although direct comparisons with other GBCAs are still needed.
“When we learned about gadopiclenol, we were interested in trying this for our lymphangiography practice for two reasons,” said Scott M. Thompson, MD, PhD, from the Department of Radiology at Mayo Clinic in Rochester, MN. “First, this new agent had some of the highest T1 shortening, which gives us potentially brighter signal. Secondly, it contains half the amount of the gadolinium ion, so we could potentially get better signal with less gadolinium.”
DCE-MRL is an MRI technique used to evaluate the structure of the lymphatic system and how lymphatic fluid moves through it. The exam works by injecting a GBCA into lymph nodes or just beneath the skin, where it enters the lymphatic vessels and makes them visible on MRI.
“However, there is concern about the retention of gadolinium-based contrast agents in patients’ bodies over time, especially in those that require repeated scans or those that are starting at a particularly young age,” Dr. Thompson said.
Seeking an alternative that could reduce gadolinium exposure without sacrificing image quality, Dr. Thompson and colleagues turned their attention to gadopiclenol, which was approved for MRI use in the U.S. in 2022 and in Europe in 2023, based on clinical studies demonstrating its safety and efficacy. However, its performance in the nodal or dermal injections used for DCE-MRL had yet to be evaluated.
Assessing Safety and Image Quality
In their study, Dr. Thompson and colleagues led a first-in-human experience involving 23 patients to test DCE-MRL with gadopiclenol. The patients had a spectrum of lymphatic pathologies and ranged in age from seven to 89 years old.
Gadopiclenol was administered via inguinal lymph node injection in all patients, and via interstitial transpedal injection for one patient. Dr. Thompson noted that the decision whether to perform inguinal or transpedal injection is driven by the clinical question being asked by the referring physician.
The team then assessed the safety of the technique and image quality.
“Surprisingly, optimization was very quick thanks to our team of medical physicists led by Dr. Eric Stinson,” Dr. Thompson said. “The team used experimental modeling to tweak the parameters on the scanner and continuously refine the imaging protocol, nearly in real time, to obtain the best signal possible.”
The team ultimately obtained diagnostic-quality images to evaluate central conducting lymphatic anatomy, flow and drainage into the central venous system. For the patient who received an interstitial transpedal injection, the images also provided visualization of superficial lymphatic anatomy in the lower extremities. The images can be used to diagnose lymphatic pathologies as well and guide subsequent intervention planning.
“We can confirm that yes, we got excellent signal, and that it was safe,” Dr. Thompson said. “There were no adverse events reported by any patient.”
Dr. Thompson said the results can have exciting implications for patient care. “One of the major advantages here is that there's half the amount of gadolinium, and we can use less contrast agent and still get diagnostic quality images,” he emphasized. “That will be key for making this method safer in the long term.”
In terms of clinical practice, Dr. Thompson and his team have already transitioned to using gadopiclenol as their standard contrast agent. “In the paper, we reported on 23 patients. Now, as of August of 2026, we've completed 75 patients total, and it's going very well,” he said.
Continued Testing Needed to Compare GBCAs
Dr. Thompson said that determining whether gadopiclenol is a superior GBCA, will require direct comparison studies. “If one really wants to do a head-to-head comparison study of GBCAs, one would image the same patient twice, each time with a different agent, for true intra-individual comparisons,” Dr. Thompson said. “But it's very hard to medically justify that."
Alternatively, he suggested a future comparative study could rely on large cohorts of individuals wherein each cohort uses a different GBCA. However, this setup presents its own challenges too. “Comparative studies across patient cohorts in the lymphatic world are challenging as there is huge variability in lymphatic pathology,” Dr. Thompson said.
“We are currently doing some preclinical studies using flow phantom models to compare agents to one another,” he added. “But our goal now is just further imaging optimization given that we’ve already shown the safety and efficacy of gadopiclenol.”
A Promising Future for MRLs
Aside from gadopiclenol, researchers and clinicians across universities are developing and testing numerous other agents to diagnose lymphatic pathologies via MRL. For example, gadoquatrane, another new GBCA, was recently approved for testing.
“Gadoquatrane is a larger molecule, about three to four times the size of existing agents, including gadopiclenol, making it large enough that we hope to see some lympho-selectivity,” said Andreas Loening, MD, PhD, from the Department of Radiology at Stanford University in California. “This could be very advantageous. The current gadolinium agents are small molecules—not lymphoselective—and therefore rapidly migrate into the blood pool, creating issues for peripheral MR lymphangiography.”
However, even with improved GBCAs, additional MRL technical challenges exist. “The lymphatic system is a one-way system, which means we need to administer contrast upstream of the area of concern,” Dr. Loening said. “This leads to challenges both with contrast administration technique as well as needing to make a priori assumptions regarding where the area of concern is.”
On top of these technical challenges, Dr. Loening said the practical limitations of MRL must also be considered. “Very few centers offer MRL,” he said. “Both central and peripheral MR lymphangiograms are relatively long exams and require interpretative expertise that the vast majority of radiologists have not had training in.”
New Initiatives Fuel Innovation
The future for MRL appears promising with the emergence of initiatives like Advanced Research Projects Agency for Health (ARPA-H) LIGHT and GLIDE, two programs focused on the lymphatic system. LIGHT refers to Lymphatic Imaging, Genomics and pHenotyping Technologies, while GLIDE refers to Groundbreaking Lymphatic Interventions and Drug Exploration.
“Lymphatic diseases have been historically underfunded relative to their prevalence from a research perspective and almost completely neglected from a medical education perspective,” Dr. Loening said. “The ARPA-H LIGHT and GLIDE programs are a unique opportunity to rapidly advance the state of the art in the diagnosis and therapy of lymphatic diseases and bring about clinically meaningful improvements for this patient population.”
With this funding, technical and practical improvements to MRL are expected to follow.
“There are several lines of work being done within the ARPA-H LIGHT that would make MRL exams technically easier to perform, provide robustness to the exams and potentially provide noncontrast techniques for quantitative assessment of lymphatic flow,” Dr. Loening said. “All of these technologies would make it easier for centers to perform MRLs and thereby expand access to patients, as well as provide additional or improved diagnostic capabilities that would translate into better patient care.”
“The combination of improved diagnostics and therapeutics will allow us to better steer care and interventions for our patients with lymphedema and other lymphatic diseases,” Dr. Loening said.
For More Information
Access the Radiology: Cardiothoracic Imaging study, “First-in-Human Safety and Feasibility of Nodal and Pedal MR Lymphangiography with Gadopiclenol.”
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