Relaxometric studies of gadolinium-functionalized perfluorocarbon nanoparticles for MR imaging

Fluorine MRI (19F MRI) is receiving an increasing attention as a viable alternative to proton-based MRI (1H MRI) for dedicated application in molecular imaging. The 19F nucleus has a high gyromagnetic ratio, a 100% natural abundance and is furthermore hardly present in human tissues allowing for hot spot MR imaging. The applicability of 19F MRI as a molecular and cellular imaging technique has been exploited, ranging from cell tracking to detection and imaging of tumors in preclinical studies. In addition to applications, developing new contrast materials with improved relaxation properties has also been a core research topic in the field, since the inherently low longitudinal relaxation rates of perfluorocarbon compounds result in relatively low imaging efficiency. Borrowed from 1H MRI, the incorporation of lanthanides, specifically Gd(III) complexes, as signal modulating ingredients in the nanoparticle formulation has emerged as a promising approach to improvement of the fluorine signal. Three different perfluorocarbon emulsions were investigated at five different magnetic field strengths. Perfluoro-15-crown-5-ether was used as the core material and Gd(III)DOTA-DSPE, Gd(III)DOTA-C6-DSPE and Gd(III)DTPA-BSA as the relaxation altering components. While Gd(III)DOTA-DSPE and Gd(III)DOTA-C6-DSPE were favorable constructs for 1H NMR, Gd(III)DTPA-BSA showed the strongest increase in 19FR1. These results show the potential of the use of paramagnetic lipids to increase 19FR1 at clinical field strengths (1.5-3T). At higher field strengths (6.3-14T), gadolinium does not lead to an increase in 19FR1 compared with emulsions without gadolinium, but leads to an significant increase in 19FR2. Our data therefore suggest that the most favorable situation for fluorine measurements is at high magnetic fields without the inclusion of gadolinium constructs. Copyright © 2014 John Wiley & Sons, Ltd.