Phase I Clinical Evaluation of Citrate-coated Monocrystalline Very Small Superparamagnetic Iron Oxide Particles as a New Contrast Medium for Magnetic Resonance Imaging

Abstract

The favorable data on the safety, tolerability, and efficacy of VSOP-C184 justify further clinical phase II and III trials as a contrast medium for MRI.

Colloidal stability of carboxylated iron oxide nanomagnets for biomedical use

“…It is likely that some cell toxicity concerns lie behind stopping -at least for the moment -of the clinical trials of VSOP-C184, the only CA@MNP product tested up-to-date. The phase I clinical evaluation terminated in 2004 [33], yet there is no information about its continuation. In the case of the three other coating molecules, direct correlation is seen between the biocompatibility and the strength of polyacid adsorption.…”

Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization

“…20,21,[33][34][35] Along with these earlier observations, our experimental evidence of rapid accumulation of IV injected VSOP as a function of histopathologic parameters of plaque instability show that VSOP is a promising candidate for clinical MR angiography and vessel wall imaging; it might allow for the simultaneous evaluation of the arterial lumen and characterization of vessel wall pathologies, and thereby might help in identifying unstable atherosclerotic plaques.…”

“…Preclinical and clinical data on these substances show that blood clearance of VSOP is faster compared to sterically stabilized USPIO. 5,20,22,28 Our findings suggest that microvesicles might be a suitable imaging target for VSOP administered as a contrast medium for the detection and characterization of atherosclerotic plaques by MRI. Microvesicles have recently been proposed to be an important surrogate marker for plaque instability.…”

“…The batch used in this study is identical to the batch used in the Phase I and Phase II clinical trials. 20,21 VSOP have been described in detail elsewhere. 20,22 Briefly, their basic properties are: a core diameter of 4 nm; hydrodynamic diameter of 7 nm; T1-relaxivity of 18.7; and T2-relaxivity of 30 L/(mmol × seconds) at 0.47 T. VSOP are stabilized with citrate, an anionic monomeric coating.…”

Synthesis and characterization of iron oxide magnetic nanoparticles

“…Hence, one of the main problems of producing a stable magnetic fl uid is preventing agglomeration during the synthesis and coating processes. Coatings used for iron oxide nanoparticles can consist of various types of molecules, for example inorganic molecules, small organic molecules, polymers and proteins [11][12][13][14].…”