Surface adherent carbohydrate bolsters contrast magnetism agents
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
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
Academic Radiology, April 2006, pp. 421-427.
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