College of Materials Science and Engineering and College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Tsinghua Laboratory of Brain and Intelligence, Tsinghua University, Beijing 100084, China.
ACS Nano. 2024 Sep 17;18(37):25647-25656. doi: 10.1021/acsnano.4c07533. Epub 2024 Aug 31.
The comprehensive evaluation of tumor vasculature that is crucial for the development, expansion, and spread of cancer still remains a great challenge, especially the three-dimensional (3D) evaluation of vasculatures. In this study, we proposed a magnetic resonance (MR) angiography strategy with interlocking stratagem of zwitterionic Gd-chelate contrast agents (PAA-Gd) for continuous monitoring of tumor angiogenesis progression in 3D. Owing to the zwitterionic structure and nanoscale molecular diameter, the longitudinal molar relaxivity () of PAA-Gd was 2.5 times higher than that of individual Gd-chelates on a 7.0 T MRI scanner, resulting in the higher-resolution visualization of tumor vasculatures. More importantly, PAA-Gd has the appropriate blood half-life (69.2 min), emphasizing the extended imaging window compared to the individual Gd-chelates. On this basis, by using PAA-Gd as the contrast agent, the high-resolution, 3D depiction of the spatiotemporal distribution of microvasculature in solid tumors formed by different cell lines over various inoculation times has been obtained. This method offers an effective approach for early tumor diagnosis, development assessment, and prognosis evaluation.
肿瘤血管的全面评估对于癌症的发展、扩张和扩散至关重要，但仍然极具挑战性，特别是对血管的三维（3D）评估。在本研究中，我们提出了一种磁共振（MR）血管造影策略，采用两性离子 Gd-螯合物对比剂（PAA-Gd）的连锁策略，用于连续监测 3D 中肿瘤血管生成的进展。由于两性离子结构和纳米级分子直径，PAA-Gd 的纵向摩尔弛豫率（）在 7.0 T MRI 扫描仪上比单个 Gd-螯合物高 2.5 倍，从而实现了更高分辨率的肿瘤血管可视化。更重要的是，PAA-Gd 的血液半衰期（69.2 分钟）适中，与单个 Gd-螯合物相比，强调了更长的成像窗口。在此基础上，通过使用 PAA-Gd 作为对比剂，获得了不同细胞系在不同接种时间形成的实体瘤中微血管时空分布的高分辨率、3D 描绘。该方法为早期肿瘤诊断、发展评估和预后评价提供了一种有效的方法。
