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.

Age-related blood half-life of particulate contrast material: experimental results with a USPIO in rats.

It has been well established in the literature that phagocytic activity in animals and humans changes with age, but this phenomenon has not yet been investigated for particulate contrast agents. The present study was therefore performed to determine the effect of age on blood half-life of a superparamagnetic iron oxide blood pool contrast agent and on the velocity of its uptake in the liver and spleen of the rat by means of magnetic resonance (MR) imaging. A total of 18 rats (group A: 214-255 g, age: 45-50 days; group B: 432-563 g, age: 100-120 days) were imaged at 1.5 T using a 3D gradient-recalled echo (GRE) sequence (TR/TE 6.6/2.3 msec; alpha 25 degrees, frontal). Images were acquired before and every 3-5 minutes for up to 30 minutes after i.v. injection of 30 micromol Fe/kg of a citrate-coated superparamagnetic iron oxide-based contrast agent (VSOP-C43). Intravenous injection of VSOP-C43 resulted in a pronounced initial signal enhancement in vessels, which decreased with a half-life of 8.4 +/- 0.9 minutes in group A and of 15.9 +/- 2. 4 minutes in group B (P < 0.01). The half-life of signal decrease was 11.6 +/- 2 minutes and 19.9 +/- 4.4 minutes in the liver (P < 0. 01) and 19.6 +/- 3.1 minutes and 26.7 +/- 5.2 minutes in the spleen (not significant). The results show that the age-related phagocytic activity has a significant effect on the circulation time and velocity of uptake of a particulate MR imaging contrast agent. This fact must be taken into consideration in both the preclinical and clinical development of particulate contrast material and in the clinical application of such agents.