Magnetic Resonance Imaging (MRI)

The synthesis and in vivo antigen targeting of a novel iron oxide compound were studied. A monocrystalline iron oxide nanoparticle (MION) was synthesized that contains a small (mean diameter, 2.9 nm +/- 0.9) single crystal core, passes through capillary membranes, and exhibits superparamagnetism. The MION was attached to antimyosin Fab (R11D10) and used for immunospecific magnetic resonance (MR) imaging of cardiac infarcts One hour after intravenous administration of MION-R11D10 in rats (100 mumol/kg), a marked decrease in the signal intensity of infarcted myocardium was observed.

In this study, the target-specific behavior of magnetic resonance (MR) imaging contrast agents directed at human hepatic asialoglycoprotein (ASG) receptors was evaluated in vitro with use of two novel assays: relaxation time measurements of incubated human cell membrane solutions and iron staining of biopsy samples. Specific uptake of ASG receptor-directed agents was demonstrated in human samples of normal liver tissue, areas of hepatitis, regenerating nodules, areas of focal nodular hyperplasia, and hepatic adenomas.

The dynamic effects of three different superparamagnetic magnetic resonance (MR) contrast agents on liver signal were evaluated with an echo-planar imaging technique. The contrast agents were (a) USPIO (ultrasmall superparamagnetic iron oxide), which has a long blood half-life and was developed for MR imaging of lymph nodes and bone marrow; (b) AG (arabinogalactan)-USPIO, an asialoglycoprotein receptor--directed iron oxide with hepatocyte uptake; and (c) AMI-25, a conventional reticuloendothelial iron oxide agent.

We have obtained multislice magnetic resonance (MR) images of the eye and calculated ocular dimensions along the three cardinal axes: antero-posterior (A-P), equatorial, and vertical. We found no difference in the shape of hyperopic (average refractive error: +3.72 D) and emmetropic eyes, both of which had an equatorial diameter longer than the A-P and vertical diameters. Myopic eyes (average refractive error: -6.54 D) were larger than hyperopic eyes, and most had the same spheroelliptical shape as that of the emmetropic and hyperopic eyes.

Receptor-directed MR contrast agents are currently being designed to improve sensitivity and specificity of MR imaging and to provide for functional MR imaging. In the current study we have synthesized a conjugate of asialofetuin (ASF), a bovine plasma protein with a known, high affinity for the hepatic asialoglycoprotein receptor, and a well defined, single crystal superparamagnetic label (monocrystalline iron oxide nanoparticle, MION).

A variety of adrenal imaging agents have been used in nuclear medicine, but no agent has been developed for magnetic resonance (MR) imaging. The authors have previously observed accumulation of aminated macromolecules in adrenal glands. They now report the synthesis of a model polymeric aminated contrast agent for enhanced MR imaging of the adrenal glands. The model agent consisted of a poly-L-lysine conjugate (molecular weight, 245 kd) that had 70% free epsilon amino groups and 30% diethylenetriaminepentaacetic acid (DTPA)-derivatized amino groups to bind indium-111 or gadolinium.

Existing paramagnetic agents and novel superparamagnetic pharmaceuticals under development promise to advance substantially the frontiers of MR imaging. Used in conjunction with ultrafast MR techniques, such as echoplanar imaging and turboFLASH (fast low-angle shot), relaxivity agents (e.g., dysprosium, gadolinium), which alter T1 characteristics of tissue protons they act on, can be used to generate quantitative maps of dynamic blood-brain barrier permeability as well as regional hemodynamic profiles of diseased heart and other organs.

We have previously described a novel monocrystalline iron oxide nanocompound (MION), a stable colloid that enables target specific MR imaging. In this study, the physicochemical properties of MION are reported using a variety of analytical techniques. High resolution electron microscopy indicates that a MION consists of hexagonal shaped electron-dense cores of 4.6 +/- 1.2 nm in diameter. This iron oxide core has an inverse spinel crystal structure which was confirmed by x-ray powder diffraction.