Novel Gadolinium-Free Ultrasmall Nanostructured Positive Contrast for Magnetic Resonance Angiography and Imaging

Nanostructured contrast agents are promising alternatives to Gd(III)-based chelates in magnetic resonance (MR) imaging techniques. A novel ultrasmall paramagnetic nanoparticle (UPN) was strategically designed to maximize the number of exposed paramagnetic sites and r1 while minimizing r2, by decorating 3 nm large titanium dioxide nanoparticles with suitable amounts of iron oxide. Its relaxometric parameters are comparable to that of gadoteric acid (GA) in agar phantoms, and the r2/r1 ratio of 1.38 at 3T is close to the ideal unitary value. The good contrast effect was confirmed by T1-weighted MR images of Wistar rats after intravenous bolus injection of UPN. Those results associated with good biocompatibility and a much longer contrast effect before renal excretion indicate its high potential as alternative blood-pool contrast agent to the GA gold standard for MR angiography, especially for patients with severe renal impairment.