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Surface adherent carbohydrate bolsters contrast magnetism agents

Aug 2006
Ashley Brenon

The benefits of using higher magnetic field strengths in biomedical MRI have driven investigators to explore possibilities for more efficient contrast agents. An ideal agent would work with several different imaging technologies, increase the likelihood of using MRI technology for molecular imaging, and be chemically modifiable to treat cancer.

Kenneth Watkin of the University of Illinois at Urbana-Champaign and Michael McDonald at Stanford University in California are studying the physicochemical and magnetic properties of nanoparticles to discover what characteristics make the most effective contrast agents. The endeavor has led to some surprising discoveries.

In the past, the researchers investigated pure small particulate gadolinium oxide, a nanoparticulate form of the gadolinium ion used in MRI, for its potential as a multimodal contrast and therapeutic agent. When they found much lower relaxivity (which decreases contrast) than expected, they embedded the particle in albumin microspheres. Though this did increase relaxivity, Watkin and McDonald hypothesized that relaxivity may be improved most effectively by tackling gadolinium’s fundamental drawback: its reactive nature.

In its unmodified form, small particulate gadolinium oxide forms inhomogeneous clumps that precipitate out of aqueous solution. Poor aggregation prevents water from entering the nucleus. In an attempt to improve solubility, the researchers coated gadolinium oxide nanoparticles with dextran.

Dextran, a surface adherent carbohydrate, was selected for its chemical versatility, its low toxicity, its biological resistance to cleavage and its utility within several technologies, including high-field MRI, optical imaging and single-photon emission computed tomography.

The scientists set out to characterize the newly formed particle to understand the relationship between its properties and the mechanism of proton relaxation enhancement.

They used a PerkinElmer spectrometer for physicochemical characterization, including an elemental analysis and evaluation of gadolinium concentration. They employed a Brookhaven Instruments particle size analyzer to determine a particle size of ~26 ± 6 nm.

High-resolution scanning transmission electron microscopy (left) and electron diffraction show the crystal lattice structure of a gadolinium particle coated with dextran.

The researchers also analyzed the sample size and morphological analysis with high-resolution scanning transmission electron microscopy on a Jeol USA microscope. In the micrographs, the particles exhibited regular crystalline lattices, which may contribute to relaxivity enhancement.

Most surprising was dextran’s effect on the magnetic properties of the particle. The investigators used a Magnet Property Measurement Systems’ magnetometer to quantify magnetic susceptibility for uncoated and coated particles. Although uncoated small particulate gadolinium oxide is paramagnetic, with an induced magnetism of 5.6 EMU/g at 1.5 T, the dextran-coated particle displays superparamagnetic behavior — 41.0 EMU/g — at the same field strength.

In addition, although the uncoated particle exhibits an inverse temperature-to-magnetism relationship, the coated particle’s magnetism increases as temperature increases.

The researchers are encouraged by the results so far, but much work remains. They will experiment with other coatings and processes to reveal additional characteristics. In vitro studies will investigate how the particle behaves within cells and how the body eliminates it. The particle may eventually be used in neutron capture therapy for the diagnosis and treatment of cancer.

Academic Radiology, April 2006, pp. 421-427.


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