Development And Evaluation Of Magnetic Resonance Contrast Agents

在过去的几年里，各种磁共振造影剂已经被开发出来用于细胞磁共振成像。一般来说，大多数用于细胞标记的造影剂都是超顺磁性氧化铁纳米颗粒(SPIO)，它们会导致周围组织的T2和T2缩短，以及T2加权MRI上的低信号区域。多功能荧光和SPIO纳米颗粒造影剂提供了利用细胞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+离子连接到噬菌体P22病毒衣壳的内部，得到了具有极高弛豫值的纳米级磁共振造影剂。P22特有的高度开窗的“wiffleball”形态确保了环境和衣壳内腔之间的水交换。P22‘wiffleball’的空腔被一个由多个DTPA-Gd络合物组成的支化低聚物功能化，从而在每个64 nm的衣壳内产生了1900个Gd3+离子。报道了在298K，0.65T(28 MHz)下，R_1离子=21.7 mm~(-1)秒~(-1)和R_1粒子=41,300 mm~(-1)秒~(-1)的高弛豫度，其R_1/R_2比为0.80，并优化了该体系的转动相关时间。建议对基于病毒衣壳的MRI造影剂的进一步改进提出具体的设计修改，用于临床翻译。

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.