Characterization of a Manganese-Containing Nanoparticle as an MRI Contrast Agent

Abstract

We present relaxivity and physicochemical data for a high relaxivity, manganese-containing, nanoparticle-based, and tumor selective MRI contrast agent, SN132D. The nanoparticles have a diameter of 5–6 nm, selected to give a compromise between renal excretion and tumor contrast, based on the Enhanced Permeability and Retention effect. The per manganese relaxivity (r1) is 24.8 ± 0.2 mm–1 Mn s–1 at 1.5 T and 37 °C in water, corresponding to per nanoparticle relaxivity of 347 ± 3 mm–1 s–1. The NMRD profiles in both water and serum showed a peak in r1 in the frequency range 20–40 MHz, which is characteristic of slowly moving paramagnetic systems. The r1 decreases when the temperature is increased from 25 °C to 37 °C, indicating fast exchange dynamics of the coordinated water molecules. The exchange time constant of the whole water molecule, τMO, was 6 ns. The r1 in serum is significantly higher than in water, due to an increase in medium viscosity and chelation of 18.9 ± 2.0 % of MnII ions to human serum components, most likely human serum albumin. The r1 is stable in the pH range 3–10. The per Mn relaxivity is among the highest reported for Mn-containing systems and far higher than those of the clinically used gadolinium-based contrast agents.