Superparamagnetic iron oxide nanoparticles (SPIO) are novel MRI contrast agents. After cellular uptake, SPIO cause a negative T2 contrast in MRI. Passive targeting strategies rely on SPIO uptake in reticuloendothelial cells by receptor-mediated phagocytosis. Active targeting employs SPIO-conjugates with specific targeting ligands which selectively bind to biomarkers on target cells. Several receptor systems are overexpressed in cancerous diseases and have been investigated as targets for ligand-directed SPIO.
We have synthesized a surface functionalized superparamagnetic iron oxide colloid whose clearance from the vascular compartment was inhibited by asialofetuin but not fetuin. Unlike other particulate or colloidal magnetic resonance (MR) contrast agents, the agent of the current communication is not withdrawn from the vascular compartment by cells of the macrophage-monocyte phagocytic system, as indicated by its selective increase in hepatic relaxation rates. Because of this we refer to this colloid as a hepatic selective (HS) MR contrast agent.
Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR) has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors.
We have compared the magnetic properties of various types of materials known to affect MR images. The materials compared were: (i) MR contrast agents based on chelates of paramagnetic metals (Gd-DTPA, Dy-DTPA); (ii) biological forms of iron (horse spleen ferritin and deoxyhemoglobin); and (iii) a superparamagnetic iron oxide (AMI-25). The properties compared were the magnetic susceptibility and the magnetization. The magnetization and susceptibility of superparamagnetic AMI-25 are far larger than that of ferritin or low molecular weight, paramagnetic chelates.
The effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we demonstrate that clinically approved iron oxide nanoparticles (Ferumoxytol) can be utilized to carry one or multiple drugs. These so called 'nanophores' retain their cargo within their polymeric coating through weak electrostatic interactions and release it in slightly acidic conditions (pH 6.8 and below).
The ultrasmall superparamagnetic iron oxide colloid BMS 180549 can be found lymph nodes by either subcutaneous (SC) or intravenous (IV) injection. With an SC injection in the front extremities, the axillary and brachial nodes attain the highest accumulations of the agent. With an SC injection in the rear extremities, the popliteal, iliac, and axillary nodes attain highest accumulations of the agent. With IV injection of the agent, the iliac, mediastinal and mesenteric nodes attain highest accumulations of the agent.
The ability to image specific molecular targets in vivo would have significant impact in allowing earlier disease detection and in tailoring molecular therapies. One of the rate-limiting steps in the development of novel compounds as reporter probes has been the lack of cell-based, biologically relevant, high throughput screening methods. Here we describe the development and validation of magnetic resonance imaging (MRI) as a technique to rapidly screen compounds that are potential MR reporter agents for their interaction with specific cellular targets.
Superior mesentric lymph nodes which lie as a chain near the small intestine are difficult to visualize in the rat with MRI either with or without the use of contrast agents. We previously demonstrated that the oral administration of an ultrasmall superparamagnetic iron oxide (AMI-227) produces a brightening of the lumen of the GI tract with a T1-weighted spin-echo pulse sequence. We have also shown that AMI-227 darkens abdominal lymph nodes.
Magnetic resonance imaging (MRI) has been successfully applied to many of the applications of molecular imaging. This review discusses by example some of the advances in areas such as multimodality MR-optical agents, receptor imaging, apoptosis imaging, angiogenesis imaging, noninvasive cell tracking, and imaging of MR marker genes.
A number of quantitative three-dimensional tomographic near-infrared fluorescence imaging techniques have recently been developed and combined with MR imaging to yield highly detailed anatomic and molecular information in living organisms (1, 2). Here we describe magnetic nanoparticle based MR contrast agents that have a near-infrared fluorescence (NIRF) that is activated by certain enzymes.
