Long-Term Magnetic Resonance Imaging of Brain Tumors Using a Simple Manganese Complex

Contrast-enhanced magnetic resonance imaging (CE-MRI) plays a pivotal role in the entire process of brain tumor diagnosis. However, safety concerns and the short imaging time window associated with clinical gadolinium (Gd)-based contrast agents limit the application of CE-MRI in brain tumors. In this study, a small-molecule manganese (Mn) chelate, Mn-PhDTA, was synthesized for long-term CE-MRI of brain tumors. Mn-PhDTA can be easily prepared through three-step reactions with an overall yield of 44% and suitable for gram-scale production. The benzene ring of Mn-PhDTA accelerates the bind to proteins, with longitudinal relaxivity increased by 1.88-fold to 5.14 mM^-1 s^-1 after binding at 3 T magnetic fields. After intravenous injection, Mn-PhDTA-enhanced CE-MRI significantly improved the contrast-to-noise ratios of gliomas. Furthermore, the enhancement persisted for 72 h, which is tens of times longer than that of clinical Gd-DTPA. Mn-PhDTA offers a promising alternative to Gd-based agents for the early detection of brain tumors.