Study Of Novel T₁-T₂ Dual Modal Magnetic Resonance Imaging Contrast Agents Based On Magnetic Nanoparticles

In molecular imaging and clinical diagnosis, magnetic resonance imaging （MRI） hold an extreamly important position due to its non-invasive character, superior resolution, strong soft tissue contrast, and it is capable of producing three-dimensional imaginges without penetration depth limitation. There are two types of traditional CAs, T1-positive CAs and T2-negative CAs. T1 CAs can provide brighter signals, which makes it easily and clearly to define the regions of interest （ROI）. Gd（III） possessing seven unpaired electrons is widely applied as T1 contrast component. However, the clinically used Gd-DTPA suffers from short body circulation time due to its low molecular weight. Superparamagnetic iron oxide nanoparticles （SPIOs） are classic T2 CAs. However, clinical applications of T2 CAs are still quite limited due to their inherent darkening contrast effect and magnetic susceptibility artefacts. Therefore, there is an urgent need to overcome the limitations of single imaging modality and T1-T2 dual modal imaging strategy satisfied the urgent requirement. The key of dual modal MRI strategy is its complementary advantages, striving to provide complementary imaging information to highly improve diagnostic accuracy.Magnetic nanoparticles have both excellent magnetic properties and good biological safety and facile modification ability. Therefore, dual modal MRI CAs based on magnetic nanoparticles have attract considerable interest. In this thesis, focusing on the important subject of the design of new-type T1-T2 dual modal MR CAs, we mainly completed the synthesis and characterization of novel core/shell Fe₃O₄/Gd₂O₃ nanocubes, measured their r1 and r2, and confirmed the T1-T2 dual modal contrast ability in rat liver imaging at 3.0 T.Around the subject, we mainly carried out the following work:firstly, we synthesized 9 nm core/shell Fe₃O₄/Gd₂O₃ nanocubes, which was based on Fe3O4 nanoparticles with Gd2O3 embedded in the shell, via one-step thermal decomposition approach. TEM, XRD, SQUID etc. confirmed the structure and composition of our Fe₃O₄/Gd₂O₃ nanocubes. Secondly, the determined r1 and r2 value of dopamine coated Fe₃O₄/Gd₂O₃ nanocubes at 1.5 T were as high as 45.24 and 186.51 mM-1s-1, respectively. Finally, we successfully applied our Fe₃O₄/Gd₂O₃ nanocubes in dual modal MR imaging of small animal livers at 3.0 T. In addition, we evaluated the contrast effect of our Fe₃O₄/Gd₂O₃ nanocubes at 9.4 T and found they exhibited T2-dominated contrast ability.Compared our unique Fe₃O₄/Gd₂O₃ nanocubes with spherical nanoparticles having the similar volumes, they have larger effective radius and surface area-to-volume ratio. While Gd atoms collected on the surface facilitate their chemical interaction and exchange with water protons. The embedding structure of Fe3O4 and Gd2O3 components can synergistically enhance T1 and T2 relaxation. In summary, our core/shell Fe₃O₄/Gd₂O₃ nanocubes could be potentially utilized as T1-T2 dual modal MR CAs for a wide range of theranostic applications. Meanwhile, the novel structure provided a new strategy for development of new-type T1-T2 dual modal MRI CAs.