Ovarian cancer antigen 183B2 monoclonal antibody conjugated to ultrasmall superparamagnetic iron oxide nanoparticles

Excerpt

Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used in imaging because of their abundance in water molecules, which comprise ~80% of most soft tissue. The contrast of proton MRI depends primarily on the density of the nucleus (proton spins), the relaxation times of the nuclear magnetization (T1, longitudinal; and 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 development 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 nanoparticles and other iron oxide formulations affect T2 primarily and lead to decreased signals. On the other hand, paramagnetic T1 agents, such as gadolinium (Gd³⁺) and manganese (Mn²⁺), accelerate T1 relaxation and lead to brighter contrast images.

The superparamagnetic iron oxide (SPIO) structure is composed of ferric iron (Fe³⁺) and ferrous iron (Fe²⁺). The iron oxide particles are coated with a protective layer of dextran or another polysaccharide. 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. A variety of cells can also be labeled with these particles for cell trafficking and tumor-specific imaging studies. SPIO agents are classified by their sizes with coating material (~20–3,500 nm in diameter) as large SPIO nanoparticles, standard SPIO nanoparticles, ultrasmall SPIO (USPIO) nanoparticles, and monocrystalline iron oxide nanoparticles (1).

USPIO is composed of iron nanoparticles with diameters of 4–6 nm, and the hydrodynamic diameters with dextran or polyethylene glycol (PEG) coating are 20–50 nm. USPIO nanoparticles have a long plasma half-life because of their small size. The blood pool half-life is calculated to be ~24 h in humans (2) and 2 h in mice (3). Because of its long blood half-life, USPIO can be used as a blood pool agent during the early phase of intravenous administration (4). In the late phase, USPIO is suitable for the evaluation of RES in the body, particularly in the lymph nodes (5). Various ligands and antibody-conjugated USPIO nanoparticles have been studied for in vivo targeted MRI in small animals (6, 7). Qian et al. (8) have identified ovarian cancer antigen OC183B2 on SKOV-3 human epithelial ovarian carcinoma cells and obtained its monoclonal antibody, OCMab183B2. Quan et al. (9) coupled OCMab183B2 to USPIO nanoparticles for in vivo MRI of ovarian cancer in mice.