CORVALLIS, Ore. – Scientists at Oregon State University have filed a patent on a design for a new magnetic resonance imaging contrast agent with the potential to outperform current agents while being less toxic to patients and more environmentally friendly.
The new material is based on a structure known as a metal-organic framework or MOF, whose development in the 1990s earned this year's Nobel Prize for chemistry as MOFs' many possible uses become increasingly apparent.
MOFs are made up of positively charged metal ions surrounded by organic "linker" molecules. They have nanosized pores and can be designed with a variety of components that determine the MOF's properties.
Researchers led by Kyriakos Stylianou of the OSU College of Science say their novel manganese-based MOF, which they named BVR-19, is a promising alternative to currently used contrast agents based on gadolinium. BVR is an abbreviation for beaver, OSU's mascot.
A contrast agent, also called a contrast medium, is a substance that enhances the visibility of tissues during medical imaging. Globally, the MRI contrast agent industry has an estimated value of more than $1.5 billion and is expected to grow by $750 million over the next five years amid rising demand for non-invasive diagnostic procedures.
Gadolinium is a rare earth element that comes with concerns regarding toxicity to patients, potential harm to the environment, and supply chain issues given that China accounts for many of the rare earth reserves and much of the processing and production capacity.
Manganese, however, is plentiful in the earth's crust. In addition to being used in making batteries, steel and ceramics, manganese is vital for human health in trace amounts, playing roles in antioxidation, bone formation and the metabolism of cholesterols, carbohydrates and amino acids.
"BVR-19 represents a paradigm shift in MRI contrast agent design," said Stylianou, who directs the OSU's Materials Discovery Laboratory, or MaD Lab. "We're replacing toxic metals with abundant, biocompatible ones, without compromising performance."
Gadolinium has been used in contrast agents for nearly 40 years, he said. The body doesn't metabolize the contrast agents, so they pass nearly unchanged into wastewater systems and are resistant to degradation in treatment plants. Their long-term ecotoxicological effects not well understood.
There is also risk, Stylianou said, from gadolinium retention in the body . Most agents are designed to be excreted within 24 hours of administration, but even in patients with normal kidney function, gadolinium can stay in tissues for months or years. Retention hasn't been conclusively linked to disease, but the Food and Drug Administration has issued warnings and requires patient education because of uncertainty regarding long-term consequences.
BVR-19 is the first manganese-based MOF to incorporate L-cystine, a naturally occurring, biocompatible amino acid, Stylianou said. Its synthesis takes place in water at room temperature, no toxic solvents or other harsh conditions are required, and tests show that it allows for brighter, clearer images at lower doses than required of current commercially available agents.
"This work underscores OSU's leadership in designing functional MOFs for medical and environmental applications and demonstrates how green chemistry and materials design can converge to create safer technologies," he said. "It bridges chemistry, toxicology and medicine, showing how collaboration across disciplines can transform fundamental discoveries into technologies that directly improve human health."
Doctoral student Jacob Lessard and undergraduate Dylan Pyle were first authors of the study, which was published in the Journal of Materials Chemistry B . Other contributing members of the MaD Lab were postdoctoral fellow Andrzej Gladysiak, doctoral student Emmanuel Musa and undergraduate Jeff Bowen.
The collaboration also included Robyn Tanguay, Lisa Truong and Siva Kolluri of the OSU College of Agricultural Sciences and Cory Wyatt of Oregon Health & Science University.
Funding was provided by OHSU and the OSU Research Academy.
