Iron oxide MR contrast agents for molecular and cellular imaging

Abstract

Molecular and cellular MR imaging is a rapidly growing field that aims to visualize targeted macromolecules or cells in living organisms. In order to provide a different signal intensity of the target, gadolinium-based MR contrast agents can be employed although they suffer from an inherent high threshold of detectability. Superparamagnetic iron oxide (SPIO) particles can be detected at micromolar concentrations of iron, and offer sufficient sensitivity for T 2 (*)-weighted imaging. Over the past two decades, biocompatible particles have been linked to specific ligands for molecular imaging. However, due to their relatively large size and clearance by the reticuloendothelial system (RES), widespread biomedical molecular applications have yet to be implemented and few studies have been reproduced between different laboratories. SPIO-based cellular imaging, on the other hand, has now become an established technique to label and detect the cells of interest. Imaging of macrophage activity was the initial and still is the most significant application, in particular for tumor staging of the liver and lymph nodes, with several products either approved or in clinical trials. The ability to now also label non-phagocytic cells in culture using derivatized particles, followed by transplantation or transfusion in living organisms, has led to an active research interest to monitor the cellular biodistribution in vivo including cell migration and trafficking. While most of these studies to date have been mere of the 'proof-of-principle' type, further exploitation of this technique will be aimed at obtaining a deeper insight into the dynamics of in vivo cell biology, including lymphocyte trafficking, and at monitoring therapies that are based on the use of stem cells and progenitors.

Water diffusion-exchange effect on the paramagnetic relaxation enhancement in off-resonance rotating frame

“…This brightness transition can significantly increase the detection sensitivity for theT 2 -type paramagnetic agents. This in vivo finding confirmed our previous in vitro studies on the MIONs [35], suggesting that T 1ρ -weighted imaging provides a promising method to overcome the "black holes" effect caused by the super-paramagnetic iron oxide (SPIO) in following the cellular or molecular events [36]. This result also highlights a possibility of acquiring angiography images without using paramagnetic agents.…”

Bifunctional Gold Nanoshells with a Superparamagnetic Iron Oxide−Silica Core Suitable for Both MR Imaging and Photothermal Therapy

“…Another class of inorganic nanoparticles, superparamagnetic iron oxide (SPIO) nanoparticles, have shown great promise in magnetic resonance imaging (MRI) 7 , 8 . SPIO nanoparticles have a high transverse relaxivity, r 2 , which results in negative contrast on T 2 -weighted images.…”

Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs

“…The high susceptibility difference between CA and surrounding tissue can be exploited to generate a negative contrast, and several studies have indeed demonstrated that SPIO labeling allows the detection of grafted cells in vivo with high sensitivity. 21,22 A serious issue is the particulate nature of SPIOs, which make them a target for phagocytosis by activated reticulo-histiocytic cells. SPIOs have sizes ranging from 120 to 180 nm.…”