The industry has made yet another breakthrough in the quest to find an alternative to gadolinium-based contrast agents.

Researchers at the Institute for Basic Science in South Korea developed a nontoxic contrast agent for MR and MR angiography that may be superior to gadolinium.

"Current clinically-used gadolinium-based contrast agents have intrinsic toxicity limitations, including nephrogenic systemic fibrosis from leached free Gd3+ ions in patients with renal function impairment, and gadolinium accumulation in the brain as well as skeletal system," Taeghwan Hyeon, director of the Center for Nanoparticle Research within IBS, told HCB News.

Contrast agents based on iron oxide nanoparticles are typically not used because the results they generate can be difficult to read. It's easy to see gadolinium since it appears white, but distinguishing iron oxide from air, hemorrhage, calcification, metal deposition and blood clots can be a challenge.

For instance, when imaging a patient with Alzheimer's disease, iron oxide in the blood vessels appears black and the amyloid plaques show up gray. That makes it hard to recognize the plaques from the background.

This occurs because gadolinium is a T1-type contrast agent and current iron oxide contrast agents are T2. But the research team at IBS did something new, and created ultrasmall T1 iron oxide nanoparticles called PEG-IONCs.

"Small-sized iron oxide nanoparticles exhibit good paramagnetic property, which is a required property for T1 positive MR contrast agents, and they showed good T1 MR performance," said Hyeon.

They tested the PEG-IONCs on large animals, including rabbits, beagles, and macaque monkeys. Experiments could not be done on mice because the results wouldn't directly translate to humans.

Hematological and tissue compatibility studies in macaque monkeys demonstrated that PEG-IONCs are highly biocompatible. Current iron oxide contrast agents have to be slowly infused to reduce the risk of hypotension and other serious side effects, but PEG-IONCs can be administered without trouble.

The research team then conducted more challenging dynamic imaging on dogs and monkeys to see the vascular flow patterns of cerebral ischemia, which causes stroke.

Images were captured every 1.5 seconds after the PEG-IONCs were injected in order to see the blood perfusion patterns in the brain. The team was successful in detecting an occlusion in the middle cerebral artery.

"Extensive uses and eventual replacement [largely] depend on how serious the toxicity issues of currently clinically-used gadolinium-based contrast agents are," said Hyeon. "But at least PEG-IONCs will replace some applications of gadolinium-based contrast agents, including diagnosis of stroke and other brain diseases such as tumors, in which vascular and perfusion MR imaging are clinically important."

But he cautions that more rigorous preclinical and clinical evaluations are needed to confirm this.