Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects.

The ability to detect meniscus defects by magnetic resonance arthrography (MRA) can be highly variable. To improve the delineation of fine tears, we synthesized a cationic gadolinium complex, (Gd-DOTA-AM4 )(2+) , that can electrostatically interact with Glycosaminoglycans (GAGs). The complex has a longitudinal relaxivity (r1) of 4.2 mM(-1) s(-1) and is highly stable in serum. Its efficacy in highlighting soft tissue tears was evaluated in comparison to a clinically employed contrast agent (Magnevist) using explants obtained from adult bovine menisci. In all cases, Gd-DOTA-AM4 appeared to improve the ability to detect the soft tissue defect by providing increased signal intensity along the length of the tear. Magnevist shows a strong signal near the liquid-meniscus interface, but much less contrast is observed within the defect at greater depths. This provides initial evidence that cationic contrast agents can be used to improve the diagnostic accuracy of MRA. Copyright © 2016 John Wiley & Sons, Ltd.

Iron chelator-based amplification strategy for improved targeting of transferrin receptor with SPIO.

A major obstacle faced by magnetic resonance (MR) as a platform for molecular imaging is the low sensitivity for detecting receptor-targeted MR contrast agents. The versatility of MR imaging, however, could be improved if there existed a strategy to upregulate the receptor of interest prior to administration of the targeted contrast agent. Here, we describe an amplification strategy that uses iron chelators to upregulate the transferrin receptor (TfR) prior to administration of TfR-targeted superparamagnetic iron oxide nanoparticles (SPIO). When K562 human leukemic cells were incubated with the iron chelator desferrioxamine (DFO), followed by administration of anti-TfR SPIO, there was a 57% improvement in the T2 relaxation time compared with cells not treated with DFO and an 82% improvement compared with cells not targeted with SPIO. The effects of incubation time, temperature, SPIO concentration and targeting molecule on contrast enhancement were also examined. The results reported here suggest that iron chelators have the potential to significantly improve the sensitivity of TfR-mediated cancer detection, providing a new paradigm for MR signal amplification.