There is a great demand to develop high-relaxivity nanoscale contrast agents for magnetic resonance (MR) angiography with high resolution. However, there should be more focus on stability, ion leakage and excretion pathway of the intravenously injected nanoparticles, which are closely related to their clinic potentials. Herein, uniform ultrasmall-sized NaGdF₄ nanocrystal (sub-10 nm) was synthesized using a facile high temperature organic solution method, and the nanocrystals were modified by a ligand-exchange approach using PEG-PAA di-block copolymer. The PEG-PAA modified NaGdF₄ nanocrystal (denoted as ppNaGdF₄ nanocrystal) exhibited a high r₁ relaxivity which was twice of commercially used gadopentetate dimeglumine (Gd-DTPA) injection. MR angiography on rabbit using ppNaGdF₄ nanocrystal at a low dose showed enhanced vascular details and long circulation time. Lyophilized powder of ppNaGdF₄ nanocrystals have been successfully prepared without aggregation or reduction of MR performance, indicating the stability and an effective way to store this nanoscale contrast agent. No haemolysis was induced by ppNaGdF₄ nanocrystal, and an extremely low leakage of gadolinium ions was confirmed. Furthermore, efficient renal excretion was one of the clearance pathways of ppNaGdF₄ nanocrystal according to both the time dependent distribution data in blood and tissues and MR images. The in vivo toxicity evaluation further validated the great potential as a clinical agent for blood pool imaging.

迫切需要开发高分辨率的用于磁共振（MR）血管造影的高松弛度纳米级造影剂。然而，应该更加关注静脉注射纳米颗粒的稳定性，离子泄漏和排泄途径，这与其临床潜力密切相关。在此，使用简便的高温有机溶液法合成了均匀的超小尺寸的NaGdF ₄纳米晶体（小于10 nm），并使用PEG-PAA二嵌段共聚物通过配体交换方法对纳米晶体进行了改性。PEG-PAA修饰的NaGdF ₄纳米晶体（表示为ppNaGdF ₄纳米晶体）显示出较高的r ₁松弛度是商业上使用的ado戊二酸酯二葡甲胺（Gd-DTPA）注射的两倍。在低剂量下使用ppNaGdF ₄纳米晶对兔进行的MR血管造影显示，血管细节增强，循环时间长。已成功制备了ppNaGdF ₄纳米晶体的冻干粉末，而没有聚集或降低MR性能，这表明了稳定性和有效的方法来存储这种纳米级造影剂。ppNaGdF ₄纳米晶体未引起溶血，并且confirmed离子的泄漏极低。此外，根据血液和组织中随时间变化的分布数据和MR图像，有效的肾脏排泄是ppNaGdF ₄纳米晶体的清除途径之一。这体内毒性评估进一步验证了其作为血池成像临床剂的巨大潜力。