Very Small Superparamagnetic Iron Oxide Particles Research Articles

Monomer-coated very small superparamagnetic iron oxide particles as contrast medium for magnetic resonance imaging: preclinical in vivo characterization.

Preclinical in-vivo characterization of a newly developed MR contrast medium consisting of very small superparamagnetic iron oxide particles (VSOP) coated with citrate (VSOP-C184). VSOP-C184 (core diameter: 4 nm; total diameter: 8.6 nm; relaxivities in water at 0.94 T (T1) 20.1 and (T2) 37.1 l/[mmol*sec]) was investigated to determine its pharmacokinetics, efficacy, acute single dose toxicity, repeated dose toxicity, and genotoxicity. The plasma elimination half-life at 0.045 mmol Fe/kg was 21.3 +/- 5.5 minutes in rats and 36.1 +/- 4.2 minutes in pigs, resulting in a T1-relaxation time of plasma of < 100 milliseconds for 30 minutes in pigs. The particles are mainly cleared via the phagocytosing system of the liver. MR angiography at a dose of 0.045 mmol Fe/kg shows an excellent depiction of the thoracic and abdominal vasculature in rats and of the coronary arteries in pigs. The LD50 in mice is > 17.9 mmol Fe/kg. A good tolerance and safety profile was found. The experiments indicate, that VSOP-C184 may be a well tolerated and safe contrast medium for MR imaging that can be effectively used for MR angiography including visualization of the coronary arteries.

Preclinical Characterization of Monomer-Stabilized Very Small Superparamagnetic Iron Oxide Particles (VSOP) as a Blood Pool Contrast Medium for MR Angiography

All SPIO particles that have so far undergone preclinical or clinical testing are coated with an organic polymer such as dextran (1), carboxydextran (2,3), or polyethylene glycol (4). Polymer coating limits the minimal overall particle size that can be achieved. However, the pharmacokinetic and physical properties resulting from a small particle size appear to offer advantages for MR angiography (1). The present article is based on a project in which a manufacturing procedure for coating iron oxide particles with monomeric material was developed (5,6). This procedure allows for producing so-called very small superparamagnetic iron oxide particles (VSOP). Using this procedure, particles with a citrate coating and an overall particle size of 8 nm were produced (VSOP-C184) in order to develop an iron-oxide-based blood pool contrast medium for MR angiography (7,8). This study presents results of a preclinical in vivo characterization of VSOPC184 in terms of toxicity, pharmacokinetics, and efficacy as a contrast medium for vascular MR imaging. MATERIALS AND METHODS

New generation of monomer-stabilized very small superparamagnetic iron oxide particles (VSOP) as contrast medium for MR angiography: preclinical results in rats and rabbits.

The purpose of this study was to evaluate the signal enhancement characteristics of very small superparamagnetic iron oxide particles (VSOP)-C63, a new monomer-coated, iron oxide-based magnetic resonance (MR) blood pool contrast medium with a very small particle size and optimized physical properties. Equilibrium MR angiography (MRA) of rats (thoracic and abdominal vessels) was performed at 1.5 T with a three-dimensional gradient-recalled echo (3D GRE) technique (TR/TE 6.6/2.3 msec, flip angle 25 degrees ) before and after (every 3-5 minutes up to 50 minutes) i.v. injection of VSOP-C63 [dosages: 15, 30, 45, 60, 75, and 90 micromol Fe/kg; diameter: 8 nm; relaxivities at 0.47 T: R1 = 30 l/(mmol * s); R2 = 39 l/(mmol * s)]. First-pass MRA images (3D-GRE, TR/TE 4.5/1.7 msec, flip angle 25 degrees ) were obtained with 45 micromol Fe/kg VSOP-C63 in comparison with 0.2 mmol Gd/kg of gadolinium diethylene triamine pentaacetic acid (Gd DTPA; before and every 5 seconds p.i.). MRA (3D GRE, TR/TE 4.5/1.7 msec, flip angle 25 degrees) of coronary vessels in rabbits was performed after i.v. injection of 45 micromol Fe/kg of VSOP-C63. In rats maximal S/N ratio in thoracic and abdominal arteries directly after i.v. injection of VSOP-C63 was 25 +/- 1, 43 +/- 2, 49 +/- 4, 57 +/- 3, 64 +/- 3, and 63 +/- 3 for the different dosages. Blood half-life was dose dependent (15 +/- 2, 20 +/- 3, 29 +/- 6, 37 +/- 5, 61 +/- 16, and 86 +/- 21 minutes). At a dose of 30 micromol Fe/kg even small intrarenal arteries were sharply delineated. First-pass MRA showed no significant difference in the S/N ratio between Gd-DTPA (71.5 +/- 11.5) and VSOP-C63 (65.1 +/- 18. 3). The proximal segments of the coronary arteries in rabbits were clearly depicted at a dose of 45 micromol Fe/kg. The monomer-coated, iron oxide-based contrast medium VSOP-C63 exhibits favorable properties as a blood pool agent for both equilibrium and first-pass MRA. J. Magn. Reson. Imaging 2000;12:905-911.