At the European Congress of Radiology in Vienna, GE HealthCare announced it has completed recruitment for Phase I of its early clinical trial for a first-of-its-kind manganese-based macrocyclic MR contrast agent.

Manganese-based contrast agents have comparable relaxivity to typical gadolinium-based agents for enhancing signal intensity during MR scans, but gadolinium retention concerns have led manufacturers to invest in making alternative agents with less or no gadolinium.

Manganese is endogenous, making it a naturally-occurring trace element that can be efficiently eliminated from the body. GE HealthCare expects it to be diagnostically similar to GBCAs.
And whereas previous manganese-based MR agents have a “free manganese” release mechanism, this investigational agent is tightly bound to the chelate, in a macrocyclic cage-like structure. This quickly eliminates it, rather than releasing it inside of the body.

Based at Oslo University Hospital, Rikshospitalet, Norway, the trial will evaluate the agent’s safety profile and how injections of it are eliminated from the body in healthy subjects.

“This manganese-based MR agent is one of a number of novel agents we have at various stages of development in our innovation pipeline, all of which aim to give practitioners more choice in delivering precision care for their patients,” said Dr. Paul Evans, head of global R&D at GE HealthCare’s pharmaceutical diagnostics unit, in a statement.

GBCAs have been linked to issues in people with advanced kidney failure and renal insufficiency, including nephrogenic systemic fibrosis, a painful and often fatal disease characterized by thickening and darkening of the skin and organs. In the last decade, evidence has emerged suggesting that gadolinium also accumulates in the brain and can lead to gadolinium deposition disease in people with normal renal functioning.

While no adverse impacts have been found, the FDA now requires “black box” warnings about the heavy metal. Additionally, GBCAs increase gadolinium levels in earth’s surface waters, as patients expel it in their urine within 24 hours. When exposed to UV light, it becomes toxic. Japanese researchers emphasized this in a 2020 study after finding spikes in gadolinium throughout their city’s river waters.

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