(USPIO) The class of the ultrasmall superparamagnetic iron oxide includes several chemically and pharmacologically very distinct materials, which may or may not be interchangeable for a specific use. Some ultrasmall SPIO particles (median diameter less than 50nm) are used as MRI contrast agents (Sinerem®, Combidex®), e.g. to differentiate metastatic from inflammatory lymph nodes. USPIO shows also potential for providing important information about angiogenesis in cancer tumors and could possibly complement MRI helping physicians to identify dangerous arteriosclerosis plaques.
Because of the disadvantageous large T2*//T1 ratio, USPIO compounds are less suitable for arterial bolus contrast enhanced magnetic resonance angiography than gadolinium complexes. The tiny ultrasmall superparamagnetic iron oxides do not accumulate in the RES system as fast as larger particles, which results in a long plasma half-life. USPIO particles, with a small median diameter (less than 10 nm), will accumulate in lymph nodes after an intravenous injection by e.g. direct transcapillary passage through endothelial venules. Once within the nodal parenchyma, phagocytic cells of the mononuclear phagocyte system take up the particles.
As a second way, USPIOs are subsequently taken up from then interstitium by lymphatic vessels and transported to regional lymph nodes. A lymph node with normal phagocytic function takes up a considerable amount and shows a reduction of the signal intensity caused by T2 shortening effects and magnetic susceptibility. Caused by the small uptake of the USPIOs in metastatic lymph nodes, they appear with less signal reduction, and permit the differentiation of healthy lymph nodes from normal-sized, metastatic nodes.

See also Superparamagnetic Contrast Agents, Superparamagnetic Iron Oxide, Very Small Superparamagnetic Iron Oxide Particles, Blood Pool Agents, Intracellular Contrast Agents.

Blood pool agents (intravascular contrast agents) remain in the blood for a prolonged time compared with conventional contrast agents, which diffuse quickly into the interstitial space. Magnetic resonance angiography (MRA), cardiovascular imaging, or contrast enhanced MRIs are possible over an hour or more. This advantage over conventional MRI contrast media allows also higher resolution MRA of several territories using respiratory or cardiac gating techniques with a single contrast bolus.
Different types of blood pool contrast agents:
Blood pool MRI contrast agents with their longer intravascular circulation can be designed to be targeted to necrotic myocardium, to assess myocardial viability, or tumor directed to provide better diagnostic information for various tumors. A disadvantage of the use of blood pool agents for MRA is that the separation of arteries and veins is more difficult because they are present in both and the overlapping of those vessels is disturbing. This can be solved by e.g. different MIP segmentation algorithms.

See also Necrosis Avid Contrast Agent, Tumor Specific Agents, Feruglose, Gadofosveset Trisodium (Vasovist), Ultrasmall Superparamagnetic Iron Oxide and Contrast Medium.

Contrast agents are chemical substances introduced to the anatomical or functional region being imaged, to increase the differences between different tissues or between normal and abnormal tissue, by altering the relaxation times. MRI contrast agents are classified by the different changes in relaxation times after their injection.
The design objectives for the next generation of MR contrast agents will likely focus on prolonging intravascular retention, improving tissue targeting, and accessing new contrast mechanisms. Macromolecular paramagnetic contrast agents are being tested worldwide. Preclinical data shows that these agents demonstrate great promise for improving the quality of MR angiography, and in quantificating capillary permeability and myocardial perfusion.
Ultrasmall superparamagnetic iron oxide (USPIO) particles have been evaluated in multicenter clinical trials for lymph node MR imaging and MR angiography, with the clinical impact under discussion. In addition, a wide variety of vector and carrier molecules, including antibodies, peptides, proteins, polysaccharides, liposomes, and cells have been developed to deliver magnetic labels to specific sites. Technical advances in MR imaging will further increase the efficacy and necessity of tissue-specific MRI contrast agents.

See also Adverse Reaction and Nephrogenic Systemic Fibrosis.

See also the related poll result: 'The development of contrast agents in MRI is'

Short name: Ami 227, generic name: Ferumoxtran, (USPIO)
Ferumoxtran is a substance of the class of ultrasmall superparamagnetic iron oxide used as a lymph node specific contrast agent for MRI.
See also Combidex®, Sinerem® and Ultrasmall Superparamagnetic Iron Oxide.
Partner(s): Cytogen Corporation, National Cancer Institute. An approvable letter was received from the U.S. Food and Drug Administration for Combidex in June 2000. Advanced Magnetics, Inc. has submitted a complete response to the approvable letter received from the U.S. Food and Drug Administration, which was accepted by the FDA and assigned a user fee goal date of March 30, 2005. In Europe, a Dossier (the European equivalent of a NDA) was submitted by Advanced Magnetics' European partner, Guerbet SA, to the European Medicines Evaluations Agency in December 1999. (Sinerem® is the brand name for this USPIO in Europe manufactured by Guerbet, Combidex® by Advanced Magnetics for the U.S. market)
Advanced Magnetics, Inc. changed its name in July 2007 to AMAG Pharmaceuticals Inc.

Contrast agent with a preferential intracellular distribution.
Intracellular agents (such as manganese derivatives and ultrasmall superparamagnetic iron oxide), exhibit a flow- and metabolism-dependent uptake. These properties may allow delayed imaging, similar to isotopic methods.
Phospholipid liposomes are rapidly sequestered by the cells in the reticuloendothelial system (RES), primarily in the liver. For imaging of the liver, liposomes may be labeled with MR contrast medium, both positive (T1-shortening) paramagnetic media, and negative (T2-shortening) superparamagnetic media.
Several other nonliposome MR contrast media are also taken up by the RES, e.g.:
Other MR contrast agents accumulate selectively in the hepatocytes, e.g.: