Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used to create images because of their abundance in water molecules, which comprise >80% of most soft tissues. The contrast of proton MRI images depends mainly on the density of nuclear proton spins, the relaxation times of the nuclear magnetization (T1, longitudinal; T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the use of contrast agents. Most contrast agents affect the T1 and T2 relaxation times of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (1). Cross-linked iron oxide (CLIO) and other iron oxide formulations affect T2 primarily and lead to a decreased signal. On the other hand, paramagnetic T1 agents, such as gadolinium (Gd) and manganese (Mn), accelerate T1 relaxation and lead to brighter contrast images. The superparamagnetic iron oxide (SPIO) structure is composed of ferric iron (Fe) and ferrous iron (Fe). These particles have large combined magnetic moments or spins, which are randomly rotated in the absence of an applied magnetic field. SPIO is used mainly as a T2 contrast agent in MRI, though it can shorten both T1 and T2/T2* relaxation processes. SPIO particle uptake into the reticuloendothelial system (RES) is by endocytosis or phagocytosis. SPIO particles are also taken up by phagocytic cells such as monocytes, macrophages, and oligodendroglial cells. SPIO nanoparticles are sometimes modified with dextran, poly(ethylene glycol) (PEG), or other biomaterials to reduce RES uptake and to prolong blood half-life. A variety of cells can also be labeled with these particles for cell trafficking and tumor-specific molecular imaging studies. SPIO agents are classified by their sizes with coating material (~20–3,500 nm in diameter) as large SPIO (LSPIO) nanoparticles, standard SPIO (SSPIO) nanoparticles, ultrasmall SPIO (USPIO) nanoparticles, and monocrystalline iron oxide nanoparticles (MION) (1). Gold (Au) are easily added to SPIO nanoparticles with electron beam irradiation of a solution of Au and SPIO to form Au/SPIO (2). The Au moieties are highly reactive with the thiol group a strong Au-S bond. Kojima et al. (3) coated the Au/SPIO nanoparticles with a thiol-modified PEG (PEG-S) to form PEG-S-Au/SPIO nanoparticles to study tumor accumulation in tumor-bearing mice.