MRI Contrast Agent
Magnetic Resonance Imaging (MRI), or nuclear magnetic resonance imaging (NMRI), is a medical imaging technique commonly used in radiology to visualize the internal structure and function of the every part of the body, and is particularly useful for neurological conditions, for disorders of the muscles and joints, for evaluating tumors, and for showing abnormalities in the heart and blood vessels.MRI provides greater contarst between the different soft tissues of the body than computer tomography (CT) making it very useful in neurological (brain), muskuloskeletal, cardiovascular, and oncological (cancer) imaging. It uses a powerful magnetic field to align the nuclear magnetization of hydrogen atoms in water in the body without the use of ionizing radiation. The alignment of this magnetization is usually altered with radio frequency (RF) fields causing the hydrogen nuclei to produce a rotating magnetic field signal that is detected by the scanner. This signal can be enhanced by additional magnetic fields to build up enough information to construct an image of the body or the tissue. Diseased tissue, such as tumors, can be detected because the protons in different tissues return to their equilibrium state at different rates. Changing the parameters on the scanner creates a contrast between different types of body tissues.
To enhance the appearance of tissues such as blood vessel, tumors, muscles, bones, neurons, etc., contrast agents may be injected intravenously. In certain cases such as problems of the joints, the contrast agents may be directly injected into tissue to generate MR images of joints. MRI is used to image every part of the body, and is particularly useful for neurological conditions, for disorders of the muscles and joints, for evaluating tumors, and for showing abnormalities in the heart and blood vessels.
While most conventional MRI contrast agents have difficulty in providing sufficient signal amplification and versatile functionalization that is essential for target-specific molecular imaging probes, magnetic nanoparticles hold great potential to fulfill these needs. Furthermore, these are well suited as contrast agents for in vivo MRI because of their unique superparamagnetic properties, which generate a significant susceptibility effect that results in strong T2 and T*2 contrasts, as well as a T1 effect at very low concentrations. In addition to these unique properties and advantages of nanocrystals, iron oxide nanocrystals usually have a long blood retention time, generally biodegradable, and are considered to be tolerable at low concentrations.
Ocean’s superparamagnetic IO nanocrystals are suitable MRI contrast agents. These exhibit high efficient response to magnetic fields and have functional groups on the outer surface that can be linked to different types of molecules designed for target specific imaging. Ocean’s superparamagnetic IO nanocrystals offers the opportunity to design “smart” nanocrystals that can be sued as target-specific contrast agents and multi-modality imaging probes. These also offer the possibility of multi-functionalization using multiple reagents for simultaneous imaging of different tissues for diagnostic applications. Extensive research has shown that nanocrystals in the size range of 5-100 nm are taken up and accumulate preferentially in various cell lines, including cancer and tumor cells, to allow magnetic labeling of the targeted cells because of enhanced permeability and retention effect associated with cancer or tumor growth. When internalized by cells, iron oxide nanoparticles are able to generate imaging contrasts that enable the detection of a single-cell by MRI. The uptake and accumulation of Ocean’s superparamagnetic IO nanocrystals are most promising for improving the sensitivity of molecular imaging and quantitative cellular analysis by 1-2 orders of magnitude.
In comparison with dextran-coated IO nanocrystals which consist of 5-10 nm core and more than 20 nm dextran shell, Ocean NanoTech’s iron oxide nanoparticles that are 5- 30 nm in diameter with a monolayer polymer coating show similar hydrodynamic size with dextran-coated IO anocrystals. However, the inorganic core size is much larger than the core of the dextran-coated nanocyrstal, increasing the magnetic contrast.
Ocean NanoTech is actively developing a new generation of iron oxide nanocrystals for target-specific MR imaging probes. Our recent development indicate that the effective converse relaxation rate of our 30 nm IO nanocrystals is 2.5 times higher than the 10 nm nanocrystals. The in vivo studies also demonstrated that nanocrystals conjugated to affinity ligands can specifically target tumor sites (Figure 1). The detailed information can be found in our recent publication in Small and Gastroenterology.
Additional objectives that Ocean NanoTech is targeting to improve the application of superparamagnetic IO nanocrystals as MRI contrast agent include 1) emission of a strong signal to increase the sensitivity of detection while exhibiting low toxicity to healthy organs and tissues; 2) identification of a target molecule that is unique to an over expressed receptor to that will receive sufficient amount of the imaging probe; and 3) reduction of the reticuloendothelial system (RES) uptake to increase the detection sensitivity. Ocean NanoTech is actively working with collaborators to achieve the above objectives to move the application of superparamagnetic IO nanocrystals as MRI contrast agent from the research stage to clinical applications.