A new class of cubic SPIONs as a dual-mode T1 and T2 contrast agent for MRI

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as a robust negative contrast agent on conventional MRI. In this study, we (a) synthesized a new class of cubic SPIONs as a dual-mode contrast agent in MRI and (b) showed the in-vivo feasibility of these nanaoparticles as a simultaneous positive and negative contrast agent. Relaxation properties and contrast enhancement analysis of the synthesized SPIONs with two different shapes (cubic vs. spherical) and three different sizes 7 nm, 11 nm, and 14 nm were investigated to evaluate contrast enhancement in-vitro. In-vivo MRI experiments were performed on a 3T MR scanner, where a healthy anesthetized rat was imaged before, and from 20 to 80 min after intravenous injection of 1 mg/kg of contrast agent. Representative transmission electron microscopy (TEM) images of the synthesized nanoparticles reveal that the particles are well dispersed in a solvent and do not aggregate. The in-vitro relaxivity and contrast enhancement analysis show that, among all six SPIONs tested, 11-nm cubic SPIONs possess optimal molar relaxivities and contrast enhancement values, which can shorten the spin-lattice and spin-spin relaxation times, simultaneously. No noticeable toxicity is observed during in-vitro cytotoxicity analysis. In-vivo T-1 and T-2-weighted acquisitions at 60-min post-injection of 11-nm cubic SPIONs result in 64% and 48% contrast enhancement on the T-1-and T-2-weighted images, respectively. By controlling the shape and size of SPIONs, we have introduced a new class of cubic SPIONs as a synergistic (dual-mode) MRI contrast agent. 11-nm cubic SPIONs with smaller size and high positive and negative contrast enhancements were selected as a promising candidate for dual-mode contrast agent. Our proof-of-concept MRI experiments on rat demonstrate the in-vivo dual-mode contrast enhancement feasibility of these nanoparticles.