Development And Evaluation Of Magnetic Resonance Contrast Agents

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Various MRI contrast agents have been developed for cellular MR imaging over the past few years. In general most contrast agents used for cell labeling are superparamagnetic iron oxide nanoparticles (SPIO) that result in T2 and T2 shortening of the surrounding tissues and hypointense regions on T2 weighted MRI. Multifunctional fluorescent and SPIO nanoparticle contrast agents provides the ability to track labeled cells with cellular MRI and fluorescent microscopy or to determine the cells functional state (i.e., stem cell like or differentiated. We attached multiple chelated Gd3+ ions to the interior of bacteriophage P22 viral capsids afford nanoscale MRI contrast agents with extremely high relaxivity values. Highly fenestrated 'wiffleball' morphology is unique to P22 and assures water exchange between the environment and interior cavity of the capsid. The cavity of P22 'wiffleball' was functionalized with a branched oligomer comprising of multiple DTPA-Gd complexes resulting in an impressive payload of 1,900 Gd3+ ions inside each 64nm capsid. High relaxivities of r1 ionic = 21.7 mM-1 sec-1 and r1 particle = 41,300 mM-1 sec-1 at 298K, 0.65T (28MHz) are reported, with r1/r2 ratio of 0.80 and optimized rotational correlation time for this system. Specific design modifications are suggested for future improvements of viral capsid-based MRI contrast agents directed toward clinical translation.