Development of a T1 Contrast Agent for Magnetic Resonance Imaging Using MnO Nanoparticles

Abstract

Nanometer-sized colloidal particles (nanoparticles) have been extensively used in biomedical applications as a result of their many useful electronic, optical, and magnetic properties that are derived from their nanometer size and composition. Semiconductor nanoparticles (also known as quantum dots) have been applied as fluorescent probes for cell labeling in optical imaging, and gold nanoparticles derivatized with oligonucleotides have been used for sensing complementary DNA strands. Magnetic nanoparticles have been applied to contrast-enhancement agents for magnetic resonance imaging (MRI), magnetic carriers for drug-delivery systems, biosensors, and bioseparation. MRI is one of the most powerful imaging techniques for living organisms as it provides images with excellent anatomical details based on soft-tissue contrast and functional information in a non-invasive and real-time monitoring manner. MRI has further advanced by the development of contrast agents that enable more specific and clearer images and enlargements of detectable organs and systems, leading to a wide scope of applications of MRI not only for diagnostic radiology but also for therapeutic medicine. Current MRI contrast agents are in the form of either paramagnetic complexes or magnetic nanoparticles. Paramagnetic complexes, which are usually gadolinium (Gd) or manganese (Mn) chelates, accelerate longitudinal (T1) relaxation of water protons and exert bright contrast in regions where the complexes localize. For instance, gadolinium diethylenetriaminepentaacetate (Gd-DTPA) has been the most widely used of such complexes and its main clinical applications are focused on detecting the breakage of the blood-brain barrier (BBB) and changes in vascularity, flow dynamics, and perfusion. Manganese-enhanced MRI (MEMRI), which uses manganese ion (Mn) as a T1 contrast agent, is applicable to animals only owing to the toxicity of Mn when it accumulates excessively in tissues and despite the increasing appreciation of this technique in neuroscience research. The recent development of molecular and cellular imaging to help visualize disease-specific biomarkers at the molecular and cellular levels has led to an increased interest in magnetic nanoparticles as MRI contrast agents. In particular, superparamagnetic iron oxide (SPIO) has emerged as the prevailing agent so far. 10] However, the negative contrast effect and magnetic susceptibility artifacts of iron oxide nanoparticles are significant drawbacks of using SPIO in MRI. The resulting dark signal can mislead the clinical diagnosis in T2-weighted MRI because the signal is often confused with the signals from bleeding, calcification, or metal deposits, and the susceptibility artifacts distort the background image. For the extensive applications of MRI to diagnostic radiology and therapeutic medicine and to overcome the [*] Prof. J. H. Lee, Prof. S. T. Kim, Prof. S.-H. Kim Department of Radiology, Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 135-710 (Korea) Fax: (+82)2-3410-0084 E-mail: junghee42.lee@smc.samsung.co.kr