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Citrate-coated (184th variant) very small superparamagnetic iron oxide particles.


The MICAD Research Team.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2006 Sep 01 [updated 2006 Sep 27].


Superparamagnetic iron oxide (SPIO) particles are potent and versatile contrast media for magnetic resonance imaging (MRI), and their efficacy has been shown to increase as their diameter decreases (1) SPIO particles were originally developed as liver MRI contrast agents to improve tumor detection at T2-weighted imaging. Nevertheless, SPIO particles administered as a bolus (e.g., ferucarbotran (2)) only produce moderate signal enhancement, especially in the early stage of a dynamic T1-weighted MRI. Ultrasmall superparamagnetic iron oxide particles (USPIO), such as ferumoxtran-10 (3), can only be administered as an infusion. Current SPIO and USPIO particles present very limited benefits compared with the low-molecular weight gadolinium-based contrast media (4, 5), which acquire their blood pool effect by binding to plasma proteins after intravenous injection. VSOP-C184, a citrate-coated very small iron oxide paramagnetic particle (VSOP) with a T1/T2 ratio higher than most SPIO and USPIO particles studied so far (e.g., NC 100150 (6) and SHU 555 C (7)), is being investigated as a novel contrast medium for magnetic resonance angiography (MRA). First results from preclinical and phase I studies have been reported in the literature (8, 9). VSOP-C184 is the 184th variant of 200 synthesized particles in the optimization process of the core size and citrate coating, which is designed to achieve a minimum ratio of the relaxivities R1 and R2 while maximizing the blood half-life of the contrast medium. The respective values for R1 and R2 (at 0.94 T) reported by Wagner et al. (8) are 20.1 l/mmol.sec and 37.1 l/mmol.sec, respectively. VSOP-C184 has a core diameter of 4 nm and a hydrodynamic diameter of 7.0 ± 0.15 nm. Contrary to ultra SPIO particles (USPIO), which are stabilized sterically, VSOP particles are stabilized electrostatically by a complex binding mechanism between citrate and the surface of the iron particles (9).

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