| Magnetic resonance imaging (MRI) is a noninvasive technique widely used in routine clinical diagnosis and biological research to produce 3-D temporal images of whole animals with high contrast of soft tissue. Normally Gd 3+-based MR contrast agents are applied to enhance the image contrast by decreasing the water proton T1 relaxation time. However, the low sensitivity and non-specificity of clinical agents have prohibited MR imaging capability at the cellular and intracellular regime or towards a specific biological marker. To address these problems, this thesis describes the development of new MR contrast agents for intracellular calcium imaging and for highly efficient cell labeling and long term tracking.;This thesis adopted two approaches to improve upon current Gd 3+-based MR contrast agent to enhance sensitivity and cellular permeability. The first approach (chapter 3, 4, and 5) magnifies the amount of Gd 3+ loading in a single agent by covalently conjugating multiple singular Gd3+ complexes onto a substrate, which can either be the small molecule benzene, large molecule beta-cyclodextrin, or fluorescent molecule porphyrazine. Therefore, a series of new MR contrast agents with high water relaxation capability (relaxivity) were generated with simple synthetic procedures. Further, gold nanoparticles as scaffold offered by far the most versatile platform to realize the magnification of sensitivity in cell labeling and multimodality of imaging.;The second approach (chapter 2) is through the activation of the Gd 3+ agent by intracellular calcium ion. Effort has been directed into synthesizing a cell permeable calcium sensitive MR contrast agent in order to target intracellular calcium signaling. A small molecule cell transduction moiety is chosen to be conjugated to the previously reported calcium sensitive agent Gd-DOPTA. Much progress has been made in the target molecule design and procedures; however, continuous effort has yet to be made in the final synthesis and testing. |
