Researchers from the Universities of Birmingham and St Andrews, along with Diamond Light Source, have made a groundbreaking discovery of a novel copper protein binding site that has potential applications in MRI contrast agents. This discovery challenges the conventional belief that copper is unsuitable for use in MRI and could pave the way for new imaging agents with fewer risks and side effects than the currently used contrast agents.
The team created an abiological copper site bound to oxygen donor atoms within a protein scaffold, demonstrating highly effective levels of relaxivity. Relaxivity refers to the ability of a contrast agent to influence the relaxation times of protons during an MRI scan, resulting in clearer and more informative images of internal body structures.
Co-author Dr. Anna Peacock from the University of Birmingham explained that they prepared a new-to-biology copper-binding site, which showed great potential for use in contrast agents, with relaxivities equal to or even superior to the routinely used Gd(III) agents in clinical MRI. This unexpected result showcases a powerful approach for developing new imaging tools or agents.
Furthermore, copper-based imaging agents could also find applications in Positron Emission Tomography (PET) scans, which produce detailed 3-dimensional images of the body’s interior. By using an artificial coiled coil to create the copper site within a protein scaffold, the researchers achieved performance not typically associated with copper in this context.
Dr. Peacock emphasized that metal sites not found in nature offer protein designers an expanded toolbox for designing new functional systems, opening up possibilities beyond current biological capabilities.
In MRI scanning, sections of the body are exposed to a strong magnetic field, causing water molecules’ hydrogen nuclei in tissues to align with the field. The detected spin polarization magnitude is used to create the MR image but decays with a characteristic time known as the T1 relaxation time. Different tissues have distinct T1 values, contributing to contrast in MR images. Contrast agents typically alter the value of T1 of nearby water protons, enhancing image contrast and improving the visibility of internal structures. Currently, gadolinium-based contrast agents (GBCAs) are widely used, but concerns about environmental and patient safety have led researchers to explore alternatives.
While the stability of the new copper protein site requires further investigation, the study authors view their work as a promising first step toward designing new copper-based contrast agents for clinical MRI scanning.
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