1. MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou 350108, China.
2. Department of Diagnostic Radiology, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China.
3. State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Laboratory of Spectrochemical Analysis & Instrumentation, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
4. State Key Laboratory of Molecular Vaccinology and Molecular Diagnosis & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
#These authors contributed equally to this work.
Rationale: Sensitive and accurate imaging of cancer is essential for early diagnosis and appropriate treatment. For generally employed magnetic resonance imaging (MRI) in clinic, comprehending how to enhance the contrast effect of T1 imaging is crucial for improving the sensitivity of cancer diagnosis. However, there is no study ever to reveal the clear mechanism of how to enhance the effect of T1 imaging and accurate relationships of influencing factors. Herein, this study aims to figure out key factors that affect the sensitivity of T1 contrast-enhanced MRI (CE-MRI), thereby to realize sensitive detection of tumors with low dose of CAs.
Methods: Manganese oxide (MnO) nanoparticles (NPs) with various sizes and shapes were prepared by thermal decomposition. Factors impacting T1 CE-MRI were investigated from geometric volume, surface area, crystal face to r2/r1 ratio. T1 CE-MR imaging of liver, hepatic and subcutaneous tumors were conducted with MnO NPs of different shapes.
Results: The surface area and occupancy rate of manganese ions have positive impacts on the sensitivity of T1 CE-MRI, while volume and r2/r1 ratio have negative effects. MnO octahedrons have a high r1 value of 20.07 mM-1s-1 and exhibit an excellent enhanced effect in liver T1 imaging. ZDS coating facilitates tumor accumulation and cellular uptake, hepatic and subcutaneous tumors could be detected with MnO octahedrons at an ultralow dose of 0.4 mg [Mn]/kg, about 1/10 of clinical dose.
Conclusions: This work is the first quantitative study of key factors affecting the sensitivity of T1 CE-MRI of MnO nanoparticles, which can serve as a guidance for rational design of high-performance positive MRI contrast agents. Moreover, these MnO octahedrons can detect hepatic and subcutaneous tumors with an ultralow dose, hold great potential for sensitive and accurate diagnosis of cancer with lower cost, less dosages and side effects in clinic.
Keywords: factors affecting T1 CE-MRI, sensitive tumor imaging, zwitterionic ZDS coating, ultralow dose, MnO octahedrons