Contrast-enhanced magnetic resonance angiography (CE-MRA) is a powerful technique for visualizing vascular structures and detecting thrombus. However, currently available magnetic resonance imaging (MRI) contrast agents face challenges in simultaneously achieving favorable safety profiles and prolonged diagnostic time windows. Herein, we report a polymeric manganese (Mn) chelate for highly sensitive MRA and detection of thrombus. Three polymeric Mn chelates (MnL1–3) are synthesized using hyperbranched polyethylenimine with different molecular weights. The hydrodynamic sizes of these agents (<5 nm) are below the renal filtration threshold. In vitro T1 relaxivity comparisons demonstrate that MnL3 exhibits the highest relaxivity (r1 = 6.6 mM–1·s–1 at 3 T). In vivo MRI results reveal that all three polymeric Mn chelates undergo both hepatic and renal clearance and are largely eliminated within 24 h. Notably, only MnL3 enables highly sensitive vascular imaging with a markedly extended imaging window (up to 16 min) among the three contrast agents. In a rat carotid artery thrombus model, MnL3 provides clear thrombus visualization that persists up to 16 min postinjection, whereas MnL1, MnL2, and the clinically used gadolinium (Gd)-based contrast agent Gd-DTPA allow thrombus detection only within a limited imaging time window. In addition, both in vitro and in vivo biosafety assessments demonstrate that MnL3 exhibits excellent biocompatibility. These results indicate that MnL3, with its excellent relaxivity and a relatively prolonged vascular imaging time window, shows promise for vascular disease diagnosis and may serve as a potential Gd-free MRA contrast agent.
Zhang et al. (2026) studied this question.