MRI contrast agents : current status and future perspectives

A review. Magnetic Resonance Imaging (MRI) is increasingly used in clin. diagnostics, for a rapidly growing no. of indications. The MRI technique is non-invasive and can provide information on the anatomy, function and metab. of tissues in vivo. MRI scans of tissue anatomy and function make use of the two hydrogen atoms in water to generate the image. Apart from differences in the local water content, the basic contrast in the MR image mainly results from regional differences in the intrinsic relaxation times T1 and T2, each of which can be independently chosen to dominate image contrast. However, the intrinsic contrast provided by the water T1 and T2 and changes in their values brought about by tissue pathol. are often too limited to enable a sensitive and specific diagnosis. For that reason increasing use is made of MRI contrast agents that alter the image contrast following i.v. injection. The degree and location of the contrast changes provide substantial diagnostic information. Certain contrast agents are predominantly used to shorten the T1 relaxation time and these are mainly based on low-mol. wt. chelates of the gadolinium ion (Gd3+). The most widely used T2 shortening agents are based on iron oxide (FeO) particles. Depending on their chem. compn., mol. structure and overall size, the in vivo distribution vol. and pharmacokinetic properties vary widely between different contrast agents and these largely det. their use in specific diagnostic tests. This review describes the current status, as well as recent and future developments of MRI contrast agents with focus on applications in oncol. First the basis of MR image contrast and how it is altered by contrast agents will be discussed. After some considerations on bioavailability and pharmacokinetics, specific applications of contrast agents will be presented according to their specific purposes, starting with non-specific contrast agents used in classical contrast enhanced magnetic resonance angiog. (MRA) and dynamic contrast enhanced MRI. Next targeted contrast agents, which are actively directed towards a specific mol. target using an appropriate ligand, functional contrast agents, mainly used for functional brain and heart imaging, smart contrast agents, which generate contrast as a response to a change in their phys. environment as a consequence of some biol. process, and finally cell labeling agents will be presented. To conclude some future perspectives are discussed