(275c) Magnetic Nanoparticle Composite for Dual Mode T1-T2 Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) often requires the use of contrast agents for enhanced visualization of tissue pathologies. T1 and T2 contrast agents are used to improve the T1- and T2-weighted sequences, respectively. Gadolinium-based contrast agents are used for T1 contrast enhancement, especially of fatty tissue. However, they are associated with acute nephrotoxicity. T2 contrast agents such as superparamagnetic iron oxide nanoparticles (SPIONs) are superior in imaging edema and inflammation.¹ Additionally, ultrasmall SPIONs (USPIONs) have been demonstrated to significantly enhance T1 contrast in MRI, thus preventing the nephrotoxic effects of gadolinium-based contrast agents. Development of a magnetic nanoparticle based T1–T2 dual mode MRI contrast agent can significantly improve diagnostic accuracy by providing paired anatomical images with different contrasts, and reduce drug related adverse effects. Therefore, in this study we develop SPIONs and USPIONs with enhanced contrasting ability, and combine them in situ into magnetic nanoparticle composites using flame spray pyrolysis (FSP) to obtain a dual mode T1-T2 contrast agent.

SPIONs and USPIONs were produced by FSP. The crystal size was varied between 3 to 24 nm (to yield superparamagnetic particles). The nanoparticles were coated with citrate to improve aqueous dispersibility, and characterized for their structural and magnetic properties. The T1 and T2 contrast efficiency of the nanoparticles was determined using a 9.4T Varian scanner. Finally, the SPION and USPION with highest contrasting efficiency will be combined in situ using the double-nozzle FSP technique,² and characterized for their structural, magnetic and MRI contrast enhancement properties.

Nanoparticles of sizes 3, 8, 16, and 24 nm were obtained by fine-tuning the FSP parameters. Citrate coating of the SPIONs and USPIONs significantly improved the aqueous dispersibility and stability. The largest SPION (24 nm) showed the highest saturation magnetization (55.6 emu g^-1) compared to other SPIONs, and a high T2 and T2* relaxivity of 359.4 and 409.2 mM^-1s^-1, respectively. Furthermore, the 24 nm SPIONs showed very low T1 relaxivity (0.164 mM^-1s^-1). The relaxivity values of 24 nm SPIONs indicates their effectiveness as strong T2 contrast agents.

Large SPIONs showed high T2 contrast efficiency. A double-nozzle FSP will be used to combine nanoparticles of different morphologies and contrast abilities. This study demonstrates that magnetic nanoparticle composite comprising of USPIONs and SPIONs can be used as dual mode T1-T2 contrast agent.

Acknowledgement:

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 101002582). The authors also acknowledge financial support from the Science for Life Laboratory.

References:

(1) Gee, M. S.; Harisinghani, M. G. MRI in Patients with Inflammatory Bowel Disease. J. Magn. Reson. Imaging 2011, 33 (3), 527.

(2) Grossmann, H. K.; Grieb, T.; Meierhofer, F.; Hodapp, M. J.; Noriler, D.; Gröhn, A.; Meier, H. F.; Fritsching, U.; Wegner, K.; Mädler, L. Nanoscale Mixing during Double-Flame Spray Synthesis of Heterostructured Nanoparticles. J. Nanoparticle Res. 2015, 17 (4), 1–16.