Ultra Small Iron Oxide Nanoparticle to Replace Gd Complexes as T₁ Contrast Agents for MRI

Gadolinium-based contrast agents (GBCAs) are frequently used to enhance Magnetic Resonance Imaging (MRI) contrast, which is particularly helpful in visualizing vascular structures and identifying breakdowns in the blood-brain barrier caused by conditions like tumours, abscesses, or inflammatory tissue. However, GBCAs can cause severe side effects like nephrogenic systemic fibrosis, which can lead to skin contractures, fractures, or even death. As a result, researchers are working to develop alternative T₁ contrast agents that are more biocompatible.
Iron oxide nanoparticles (IONPs) have emerged as a promising material for T₁ contrast agents, offering immense potential to improve the accuracy of MRI scans. However, IONPs have some challenges, including the need for clinical expertise in interpreting IONP-enhanced MR images and the potential for toxicity at high doses or prolonged exposure.
Using a multistage flow reactor, we developed a simple and cost-effective approach to synthesize various ultra-small single-phase iron oxide nanoparticles via the co-precipitation method. We used the principle of quenching the growth of IONPs during a fast co-precipitation synthesis combined with a partly dissolving precursor iron solution to obtain ultra small IONPs (USIONPs) with sizes up to 1.7 nm. It was found that USIONPs, particularly those less than 5 nm in size (2.7 nm and 1.7 nm), had higher r₁ values than 5 nm particles in positive contrast MRI. The r₂/r₁ ratio was approximately similar for 5 nm and 2.7 nm particles, reaching 3.4, and r₂/r₁ was 2.88 for 1.7 nm particles. These values for USIONP are in the same range as those for commercial GBCAs.
Figure 1. Phantom MR imaging of 1,7 nm IONP, Dotarem and 2.7 nm IONP with different concentration in range 0.125 - 4 mM Fe at 1.5T/T1w and 1.5T/T2w (left) and TEM images of 2.7 and 1.7 nm IONPs (right).
Reference:
Besenhard M. O., et al., (2021) Small Iron Oxide Nanoparticles as MRI T1 Contrast Agent: Scalable Inexpensive Water-Based Synthesis Using a Flow Reactor. Nanoscale. 13: 8795-8805. https://doi.org/10.1039/D1NR00877C