(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.

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: NC100150, PEG-feron, generic name: Feruglose, preliminary trade name: Clariscanâ„¢
NC100150 injection is the code name for an USPIO (ultrasmall superparamagnetic iron oxide) MRI contrast agent under development. Microvessel permeability depends on functional and morphologic characteristics of cancer vessels and on physicochemical properties of the injected contrast medium molecule.
USPIO particles have a favorable pharmacological and tolerance profile and are being tested clinically of the potential for the quantitative characterization of tumor microvasculature and specifically for measures of the microvessel permeability. Iron-based products take advantage of their large molecular size, which prevents diffusion into body tissues. These agents are disposed of by the liver and spleen as particulate matter.
NC100150 Injection (Nycomed Amersham, Amersham Health ) consists of USPIO particles that are composed of single crystals (4- to 7-nm diameter) and stabilized with a carbohydrate polyethylene glycol (PEG) coat. The iron oxide particles have to be suspended in an isotonic glucose solution. The final diameter of an USPIO particle is approximately 20 nm. Blood pool half-life is more than two hours in humans; the particles are taken up by the mononuclear phagocyte system and distributed mainly to the liver and spleen.
NC100150 would compete with the contrast agents Ferumoxytol from AMAG Pharmaceuticals, Inc. and Vasovistâ„¢ from EPIX Pharmaceuticals, Inc., but at this time the development of NC100150 Injection/Clariscan™ is discontinued.

Small particles of ferrite are used as superparamagnetic contrast medium in MR imaging (appearing predominantly dark on MRI). These agents exhibit strong T1 relaxation properties, and due to susceptibility differences to their surroundings also produce a strongly varying local magnetic field, which enhances T2 relaxation to darken the contrast media containing structures.
Superparamagnetic contrast agents are also known by the abbreviation SPIO's (small particle iron oxide or superparamagnetic iron oxide) and USPIO's (ultrasmall particle iron oxide or ultrasmall superparamagnetic iron oxide).
Two types of USPIO will be available on the market as blood pool agents, while SPIO's have been used as darkening contrast agents for liver imaging. As particulate matter they are taken up by the RES. Very small particles of less than 300 nanometers also remain intravascular for a prolonged period of time and thus can serve as blood pool agents.

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

Combidex® is the brand name (same as Sinerem®) for an ultrasmall superparamagnetic iron oxide (USPIO) in the development pipeline to detect metastatic disease in lymph nodes. Metastatic lymph nodes show less uptake of this MRI contrast agent, which results in less signal decrease and allows the differentiation of normal lymph nodes from normal-sized, metastatic nodes. Combidex® has also potential to be used as a functional molecular imaging agent.
In March 2005, AMAG Pharmaceuticals Inc received an approvable letter from the U.S. Food and Drug Administration with respect to Combidex subject to certain conditions.
See also Ferumoxtran, Drug Development and Approval Process USA, Molecular Imaging and Classifications, Characteristics, etc.