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 evalute the signal enhancement characteris tics of very small superparamagnetic iron oxide particles (VSOP)-C63, a new monomer-coated, iron oxide-based magnetic resonance (MR) blood pool contra st 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 (TRITE 6.6/2.3 msec, flip angle 25 degrees) before and afte r (every 3-5 minutes up to 50 minutes) i.v. Injection of VSOP-C63 [dosages: 15, 30, 45, 60, 75, and 90 mu mol Fe/kg; diameter: 8 nm; relaxivities at 0 .47 T: RI = 30 l/(mmol . s); R2 = 39 l/(mmol . s)]. First-pass MRA images ( 3D-GRE, TRITE 4.5/1.7 msec, flip angle 25 degrees) were obtained with 45 mu mol Fe/kg VSOP-C63 in comparison with 0.2 mmol Gd/kg of gadolinium diethyl ene triamine pentaacetic acid (Gd DTPA; before and every 5 seconds p.i.). M RA (3D GRE, TRITE 4.5/1.7 msec, flip angle 25 degrees) of coronary vessels in rabbits was performed after i.v. injection of 45 mu mol Fe/kg of VSOP-C6 3. In rats maximal SIN ratio in thoracic and abdominal arteries directly af ter 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 mu mol Fe/kg even small intrarenal arteries were sharply delineated. First-pass MRA showed no significant difference in the SIN ratio between Gd-DTPA (71.5 +/- 11.5) and VSOP-C63 (65.1 +/- 18.3). Th e proximal segments of the coronary arteries in rabbits were clearly depict ed at a dose of 45 mu mol Fe/kg. The monomer-coated, iron oxide-based contr ast medium VSOP-C63 exhibits favorable properties as a blood pool agent for both equilibrium and first-pass MRA. (C) 2000 Wiley-Liss, Inc.