Development And Evaluation Of Magnetic Resonance Contrast Agents

在过去的几年里，各种核磁共振造影剂已经被开发出来用于细胞核磁共振成像。一般来说，大多数用于细胞标记的造影剂是超顺磁性氧化铁纳米颗粒（SPIO），它会导致T2加权MRI上周围组织和低信号区域的T2和T2缩短。多功能荧光和SPIO纳米颗粒造影剂提供了通过细胞MRI和荧光显微镜跟踪标记细胞或确定细胞功能状态（即干细胞样或分化）的能力。我们将多个螯合Gd3+离子附着在噬菌体P22病毒衣壳的内部，提供了具有极高弛豫值的纳米级MRI造影剂。高度开窗的“威夫球”形态是P22独有的，确保了环境和衣壳内部腔之间的水交换。P22 ‘wiffleball’的空腔被由多个DTPA-Gd复合物组成的支链低聚物功能化，导致每个64nm的衣壳内有1,900个Gd3+离子的有效载荷。在298K， 0.65T （28MHz）下，离子r1 = 21.7 mM-1 sec-1，粒子r1 = 41300 mM-1 sec-1的高弛豫度，r1/r2比为0.80，优化了该体系的旋转相关时间。建议对基于病毒衣壳的MRI造影剂进行特定的设计修改，以指导临床转化。

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.