For these reasons, the potential for using manganese at the center of a paramagnetic complex contrast agent has always excited considerable interest. As an essential human dietary element, Mn also has essential roles in cell biology, and Mn 2+ can be used for functional brain imaging owing to the ability of Mn 2+ to enter cells through Ca 2+ channels. Mn ions possess the second-highest paramagnetic moment of any element, which is expected to have a good enhancement effect on relaxation rates 17. As a result, there is a need for clinically applicable alternatives to the current standard MR complex contrast agent that has been used for nearly 30 years. In the clinic, it is often difficult to provide accurate tumor diagnoses without contrast-enhanced MRI. Unfortunately, these nanoparticle contrast agents were never commercially launched, and their development was discontinued in recent decades due to safety concerns 12, 13 since iron-based contrast agents release free iron ions that induce the ferroptosis pathway 14, 15, 16. Superparamagnetic iron oxides have been clinically approved in the United States and Europe for liver tumor enhancement 11. The FDA also mandated that additional animal and clinical studies must be conducted to assess the safety of these agents 10. As a result, three Gd-based contrast agents lost the chance to be used in patients with kidney disease. In December 2017, the FDA ordered a black box warning on all Gd chelates in the clinic 9, 10. Additionally, Gd ions can remain in the body even after a prolonged period of time after an MRI scan 8. However, the use of some Gd chelates can result in a rare but severe complication known as nephrogenic systemic fibrosis (NSF) in patients with kidney disease 7. The sensitivity is further increased if gadolinium (Gd) contrast agents approved for human use are employed 6. Among these imaging methods, MRI has the advantage of delivering high-resolution images of brain and liver tumors without ionizing radiation and with virtually unlimited tissue penetration depth 5. Magnetic resonance imaging (MRI), ultrasound, and positron emission tomography-computed tomography (PET/CT) are most often used to evaluate deep tumors 2, 3, 4. The early diagnosis of cancers is of great importance in clinics 1. The sensitivity, accuracy and low toxicity offer by provides new opportunities for early molecular diagnostics and imaging-guided biomedical applications. Compared to the most common clinical contrast agent Magnevist, investigations in vivo demonstrate that the cross the intact blood-brain barrier of normal health mice with minor metal deposition preferentially target the glioma tissues distribute homogeneously with high penetration in an intracranial mouse model delineate clear tumor margins in MRIs of ultrasmall single-nodule brain tumors, and multi-nodular liver tumors. Here, we develop carbonized paramagnetic complexes of manganese (II) to encapsulate Mn 2+ in sealed carbonized shells with superhigh r 1 relaxivity. There is still a demand for the development of stable MRI contrast agents that exhibit higher sensitivity and superior functionality to existing contrast agents. However, these paramagnetic complexes pose some safety concerns. Paramagnetic complexes containing gadolinium ions have been widely used for magnetic resonance imaging (MRI) in clinic.
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