Synthesis, physicochemical characterization and MR relaxometry of aqueous ferrofluids

The synthesis and characterization of ferrofluid based MR contrast agents, which offer R2* versatility beyond that of ferucarbotran, is described. Ferrofluids were formed after stabilizing magnetite cores with dodecanoic acid (a), oleic acid (b), dodecylamine (c), citric acid (d) or tartaric acid (e). Core sizes were deduced from TEM micrographs. Magnetic properties were determined by SQUID magnetometry. Hydrodynamic particle diameters were determined by dynamic light scattering measurements. Zeta potentials were measured by combining laser Doppler velocimetry and phase analysis light scattering. Iron contents were evaluated colorimetrically. MR relaxometry including R1 and R2* was conducted in vitro using homogeneous ferrofluid samples. The average core diameters of ferrofluids a, b and c equaled 9.4 +/- 2.8 nm and approximately 2 nm for ferrofluids d and e. Magnetization measurements at 300 K revealed superparamagnetic behaviour for the dried 9 nm diameter cores and paramagnetic-like behaviour for the dried cores of ferrofluids d and e. Iron contents were between 32-75 mg Fe/mL, reflecting the ferrofluids' high particle concentrations. Hydrodynamic particle diameters equaled 100-120 nm (a, b and c). For the ferrofluids a, b, d and e coated with anions, strong negative zeta potential values between -27.5 mV and -54.0 mV were determined and a positive zeta potential value of +33.5 mV was found for ferrofluid c, covered with cationic dodecylammonium ions. MR relaxometry yielded R1-values of 1.9 +/- 0.3 (a), 4.0 +/- 0.8 (b), 5.2 +/- 1.0 (c), 0.124 +/- 0.002 (d) and 0.092 +/- 0.005 s(-1) mM(-1) (e), and R2*-values of 856 +/- 24 (a), 729 +/- 16 (b), 922 +/- 29 (c), 1.7 +/- 0.05 (d) and 0.49 +/- 0.05 s(-1) mM(-1) (e). Thus, the synthesized ferrofluids reveal a broad spectrum of R2* relaxivities. As a result, the various MR contrast agents have a great potential to be used in studies dealing with malignant tissue targeting or molecular imaging.