Conventional in vivo active targeting diagnostic agents commonly rely on a specific peptide or antibody, which is capable of specifically binding the target of interest, linked to a signaling agent. However, these diagnostic agents can be disadvantaged by toxicity of the conjugated peptides or antibodies and their large molecular weight may inhibit the penetration of such targeting agents through biological barriers, such as blood-brain barrier, small intestine, nasal, skin and mouth mucosa. The blood-brain barrier is one of the most stringent barriers in the human body and prevents most foreign materials from passing through. The blood brain barrier can thus severely limit the choice of diagnostic agents for neuronal diseases. The most common methods for neuronal disease diagnosis are positron emission tomography (PET) and computer tomography (CT) scans. However, these approaches are complicated and expose patients to radiation, which may increase the risk of continuous disease monitoring. In order to provide safer and longer term disease diagnosis and monitoring, new diagnostic platform technologies are needed.
Magnetic resonance imaging (MRI) is an alternative imaging technique, which is widely used in clinical settings. MRI uses magnetic fields and radio waves to generate images of the target tissue or organs in the body. Since MRI does not utilize X-rays or positron emitting radioisotopes, it is considered safer than CT and PET.
While MRI of anatomical structures and blood flow can be imaged directly, due to their natural contrast, other tissue types require the use of an MRI contrast agent for imaging. The most common MRI contrast agents are based on chelates of gadolinium. Iron- and manganese-based MRI contrast agents have also been evaluated.
MRI contrast agents, and in particular iron-based MRI contrast agents, are susceptible agglomeration and exhibit poor in vivo distribution and half-life. MRI contrast agents are typically coated with biocompatible polymers to prevent such agglomeration and to improve their in vivo distribution.
Another method for improving targeted localization of MRI contrast agents is by using targeting agents that selectively bind to the target organ or tissue of interest and also has the ability to improve the relaxivity of the contrast agent, which can also increases the magnetic resonance signal.
Notwithstanding the foregoing, there is still a need for new MRI contrast agents with improved stability and pharmacokinetics.