Design,Synthesis And Relaxivity Tuning Of Mn(Ⅲ) Porphyrin Oligomer-based MRI Contrast Agent

Magnetic resonance imaging（MRI）is one of the most powerful biological imaging technologies,it provides soft tissue contrast and functional information images based on a non-invasive and real-time manner,plays an important role in the diagnosis and localization of tumor and other diseases.In clinical applications,MRI scanning usually requires the use MRI Contrast Agents（MRICA）to change the local magnetic environment of hydrogen nuclei in the contrast area,so as to enhance image contrast and improve the visualization of tissues,organs and physiological processes.At present,gadolinium（Ⅲ）(Gd³⁺)class positive（T₁）contrast agent widely used in clinic,has some disadvantages.For example,the toxicity and side-effect are large,the relaxivity（r）of the room for improvement is small,and r₁decreases gradually with the increase of magnetic field.The development of non-gadolinium（Ⅲ）MRI contrast agents with high relaxivity,strong imaging capability and low toxicity under high magnetic field is of great significance to meet the needs of clinical diagnosis and promote the development of MRI at the level of molecular imaging and molecular tracking.Manganese porphyrins(Mn^ⅢP),whose unique molecular structure and properties give them excellent MRI enhancement effect in high magnetic field,has a prominent advantage in the innovation of new non-gadolinium-type T₁contrast agents with high sensitivity and little side effects.Based on the Solomon-Bloembergen-Morgan（SBM）equation,Mn^ⅢP oligomers with different functional groups（thiourea bonds and carbon-nitrogen double bonds）were designed,through the measurement of longitudinal relaxation time in vitro,the effects of changes in molecular volume,molecular rigid structure,and molecular configuration orientation on the longitudinal relaxivity（r₁）value of the contrast agent in the eight Mn^ⅢP molecules were discussed.The toxicity in vivo and in vitro indicated that the prepared manganese porphyrins had good biological safety in vivo,to some extent,it meets the requirements of Mn^ⅢP oligomer as diagnostic reagents.In the end,we selected p PTs and c PCNs which has the high relaxivity and good biocompatibility,and evaluate the imaging ability with MRI.The results show that positive contrast enhancement effect is most obvious in the kidneys,which can be a potential kidney-targeted contrast agent.The metabolism of the oligomer is mainly through the kidneys and liver,and it can be elimined from the body quickly,which decrease toxicity in tissues and organs.In this study,a series of Mn^ⅢP MRI contrast agents suitable for high magnetic field were obtained,and the systematic structural-activity relationship between the molecular structure and relaxivity of Mn^ⅢP was fully e xploited in this study and provided useful guidance towards more rational design of futu re Mn^ⅢP MRI probes.