High-Resolution\nMagnetic Resonance Angiography of\nTumor Vasculatures with an Interlocking Contrast Agent

The comprehensive evaluation of tumor vasculature that\nis crucial\nfor the development, expansion, and spread of cancer still remains\na great challenge, especially the three-dimensional (3D) evaluation\nof vasculatures. In this study, we proposed a magnetic resonance (MR)\nangiography strategy with interlocking stratagem of zwitterionic Gd-chelate\ncontrast agents (PAA-Gd) for continuous monitoring of tumor angiogenesis\nprogression in 3D. Owing to the zwitterionic structure and nanoscale\nmolecular diameter, the longitudinal molar relaxivity (<i>r</i><sub>1</sub>) of PAA-Gd was 2.5 times higher than that of individual\nGd-chelates on a 7.0 T MRI scanner, resulting in the higher-resolution\nvisualization of tumor vasculatures. More importantly, PAA-Gd has\nthe appropriate blood half-life (69.2 min), emphasizing the extended\nimaging window compared to the individual Gd-chelates. On this basis,\nby using PAA-Gd as the contrast agent, the high-resolution, 3D depiction\nof the spatiotemporal distribution of microvasculature in solid tumors\nformed by different cell lines over various inoculation times has\nbeen obtained. This method offers an effective approach for early\ntumor diagnosis, development assessment, and prognosis evaluation.