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.

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'

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.

A bolus is a rapid infusion of high dose contrast agent. Dynamic and accumulation phase imaging can be performed after bolus injection. Since the transit time of the bolus through the tissue is only a few seconds, high temporal resolution imaging can be required to obtain sequential images during the wash in and wash out of the contrast material and, therefore, resolve the first pass of the tracer.
For the same injected dose of contrast agent the injection rate (and, consequently, the total injected volume) modifies the bolus peak profile. Increasing the injection rate produces a sharpening of the peak (Cmax increase, Tmax decrease, peak length decrease). At a low injection rate, the first pass presents a plateau form. Substantial changes in the gadolinium concentrations during signal acquisition induce artifacts. Furthermore, the haemodynamic parameters (cardiac output, blood pressure) influence the bolus profile. The characteristics of gadolinium agents are favorable in the early bolus phase, whereas the advantages of large complexes (e.g. blood pool agents) and ultrasmall superparamagnetic iron oxide (USPIO) are most evident in the distribution phase.

An iron-based contrast agent with large molecular size, which prevents diffusion into body tissues and will be developed for MR imaging of the liver (taken up by macrophages), tumor microvasculature and microvessel permeability. The blood half live of the particles with 11-20 nm diameter is 3-4 hours.
At this time the development of Clariscanâ„¢ is discontinued.

See also NC100150 Injection and Ultrasmall Superparamagnetic Iron Oxide.