A novel blood-pooling MR contrast agent: Carboxymethyl-diethylaminoethyl dextran magnetite

Abstract

Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-Gd-based contrast agent. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. The present study evaluated whether the degree of charge alters the blood-pooling time. The evaluation was performed by injecting four groups of three Japanese white rabbits each with CMEADM-, CMEADM2-, CMEADM+ (surface charges:-10.4,-41.0 and +9.6 mV, respectively) or with ultrasmall superparamagnetic iron oxide (USPIO;-11.5 mV). The relative signal intensity (SIrel) of each was calculated using the following formula: SIrel = (SI post-contrast-SI pre-contrast / SI pre-contrast) x 100. Following injection with the CMEADMs, but not with USPIO, the in vivo pooling time was prolonged to >300 min. No significant differences were attributable to the electric charge among the CMEADM-, CMEADM2-or and CMEADM+ particles when analyzed with analysis of variance and Tukey's HSD test. Taken together, all three differently-charged CMEADM2 particles exhibited prolonged vascular enhancing effects, compared with the USPIO. The degree of charge of the contrast agents used in the present study did not result in alteration of the prolonged blood pooling time.