SPIO refers to superparamagentic iron oxide particles. They are commonly made of maghemite (Fe2O3) or magnetite (Fe3O4) having crystal-containing regions of unpaired spins. Those magnetic domains are disordered in the absence of a magnetic field. When a field is applied such as while takng an MRI, the magnetic domains align to create a magnetic moment much greater than the sum of the individual upaired electrons without resulting in residual magnetization of the particles. When injected into the blood stream, USPIO nanoparticles are taken up by macrophages and accumulate in inflamed tissues. Their iron moiety negatively enhances signal attentuation on T2-weighted images and their relative concentrations can be assessed by decreased T2-signal intensity or, more precisely, by decreased spin spin T2 relaxation time (US13/148028). The imaging capability of SPIOs is not from the SPIO intrinsically, but through their influence on longitudinal and transverse relaxation of the surrounding nuclei. In order to acheive active targeting of SPIO against specific biomolecules, it is necessary to first conjugate targeting agents onto the SPIO durface directly or onto its hydrophilic coating. An advantage of hainvg a polymer coating is that it can usually be modified to possess a variety of reactive moieties (i.e., amines, sulfydryls, carboxyls) which subsequently allow for more control over conjugation. 

Because they are superparamagnetic and because they are taken up by phagocytic cells, iron oxide particles are used as a magnetic resonance (MR) contrast agent for the exploration of the mononuclear phagocytic system. After intravenous administration of conventional superparamagentic iron oxide particles of 30-1,000-nm diameter, all of the agents are cleared from the blood within minutes, rapdily accumulating in the cells of the mononuclear phagocytic system (MPS) of liver and spleen. Ultrasmall SPIO (USPIO) particles, however, have a longer blood half-life. Weissleder (Radiology, 1990, 175, 489-493) disclose an intravenous USPIO that is not immediately recognized by the MPS of liver and spleen and thus has a longer blood half life. The small size and prolongation of the plasma half-life enabled this agent to cross the capillary wall and have more widespread tissue distribution, including uptake by the MPS of lymph nodes and bone marrow.

CR2-SPIO/USPIO nanoparticles: 

Serkova (“Renal Inflammation: Targeted Iwon Oxide Nanoparticles for Molecular MR Imging in Mice” Radiology, 255(2), 2010) disclose a recombinant protein containing the C3d-binding region of complement receptor type 2 (CR2) conjugated to the surface of an SPIO nanoparticle. Using a mouse model for lupus nephritis, they showed that after injection of the constructs into the mice and MR imaging, a significant reduction in T2 weighted MR imaging signal and T2 relaxation time was confirmed in nephritic kidneys of the mice (a significant accumulation of targeted iron oxide with a subsequent decrease in T2 relaxation times was noticed in the cortex and outer and inner medulla of the kidneys). 

USPIO have been used to detect renal inflammation in numerous animal studies as well as to detect macrophage infiltration in glomerulonephritis and renal allograft rjection in humans. Thurman (US 13/148028; see also Sargsyan, Kidney International (2012) 81, 152-159) disclose conjugating superparagmentic iron oxide (SPIO) particles and ultrasmall SPIO particles conjugated with complement receptor type 2 (CR2)-Fc which can be used as negative contrast agents for MRA for the detection of intra-renal C3b/iC3b/C3d deposits in the kidneys of mouse models for lupus nepthritis.