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New contrast agents may
be on horizon for better medical imaging
Mitchell, News Editor
photo to enlarge
by L. Brian Stauffer
by Kenneth Watkin, a professor in the department of speech and hearing science and the Beckman Institute
for Advanced Science and Technology, may lead to the
development of a new breed of “multimodal”
contrast agents that could work within a host of medical
imaging platforms – from ultrasound and computed
tomography (CT) to magnetic resonance imaging and
molecular imaging. In the screen above, right, is
a high-resolution scanning transmission electron microscope
image of dextran small particulate gadolinium oxide
(SPGO), showing the core Gd2O3 nanoparticle.
At left, is an electron diffraction pattern of dextran
— Research by scientists based at the University of Illinois at
Urbana-Champaign may lead to the development of a new breed of “multimodal”
contrast agents that could work within a host of medical imaging platforms
– from ultrasound and computed tomography (CT) to magnetic resonance
imaging and molecular imaging.
Use of these new agents may, in turn, significantly improve the diagnosis
and treatment of cancer, according to Kenneth Watkin, a professor in
the department of speech and hearing
science and the Beckman Institute
for Advanced Science and Technology.
Watkin’s findings, the result of work with former graduate student
Michael McDonald, who is now completing a postdoctoral fellowship at
Stanford University, were published recently in the journal Academic
"The goal of this work for me was to be able to create advanced
methods for the treatment of disease, specifically cancer, that reduce
the toxic effects that we see with our current treatments," Watkin
said. “And to do that, I had to develop really, really, really
" I got into this field – which is really nanomedicine –
because my area of interest is imaging and head and neck cancer,”
he said. “And as I would do imaging studies, I would see the true
devastation of chemotherapy and radiation therapy to individuals from
a psychosocial and a body point of view. So I got to thinking, ‘How
could we treat head and neck cancers differently – using fewer
The tiny carriers Watkin and McDonald are proposing would, in effect,
zero in on tumors in much the same way that smart bombs take aim at
Watkin’s transport system of choice are nanoparticles of gadolinium
The best way to visualize these nanoparticles, Watkin said, is to think
of them as “exceptionally tiny pouches.” Or better yet,
“like the trailer on a semi-truck. The deliverer is the targeting
body and the trailer is the little shell that contains the material.”
To put things in perspective: The width of a single human hair measures
about 80,000 nanoparticles.
In their work with gadolinium oxide nanoparticles, Watkin and McDonald
started by breaking nanoparticles down into even smaller particles.
Next, they successfully coated the particles with dextran, a naturally
The chemical coating – which Watkin compares to the thin, outer
shell of an M&M candy – functions as a spacer, preventing
the nanoparticle from undergoing a chemical reaction when it comes in
contact with water. It also keeps the nanoparticles from clumping and
"The M&M analogy is really a great one because it says you
can put things on the outside and you can have something on the inside,”
Watkin said. “And in the case of gadolinium oxide, it’s
really a metallic ion.”
Watkin said gadolinium oxide is a superb imaging agent because of its
superparamagnetic properties – “meaning that they work well
within a magnetic resonance imaging machine.”
Its properties as an effective emitter of radiation sources also make
it well-suited for use with a type of cancer therapy called neutron
"What it means,” Watkin said, “is that these little
particles capture the neutrons and emit alpha and gamma rays, and that
energy – sent out from an accelerator – is what can be used
to kill cancer cells.
"In looking at this, we both said, 'Holy … cow!’ These
little gadolinium particles capture neutrons at four times a greater
rate than boron, and yet boron is what is (currently) used for neutron
capture. This means it (gadolinium oxide) is potentially a multimodal
agent” … in other words, “a contrast agent that would
work with a number of different medical imaging techniques."
Among the most promising applications for using gadolinium oxide nanoparticles
as a neutron capture therapy agent is in the treatment of brain tumors.
"Treating brain tumors – typically called glioblastomas –
is very difficult,” Watkin said. “Irradiating them is really
difficult because you alter all kinds of tissues in the brain. And getting
little bubbles like this or other kinds of contrast agents into the
brain is difficult because the holes that allow plasma and other substances
to flow through the brain are very small – about 25 nanometers.
With such a small opening, you’ve got to have something pretty
tiny to get in there. So these little gadolinium oxide particles can
be really useful.”
Watkin noted that another reason the researchers initially chose to
investigate the effects of adding a dextran coating was because it makes
it possible to “target” the nanoparticle.
“By that, we mean we put a ligand – an organic substance,
such as a monoclonal antibody – on the outside that searches out
in the bloodstream. Antibodies seek their antigens. So we target something
to seek out a substance that’s expressed by cells – cancer
cells, in my work. Cancer cells express particular antigens to which
an antibody attaches itself. So, if we put the appropriate glioblastoma
antibody on the end of a particle, as it passes through the bloodstream
it will attach to the tumor cell.”
In experiments with other types of nanoparticles, Watkin has loaded
the particles with cancer-fighting drugs such as Doxorubicin or Taxiter.
He also is investigating using them to deliver genetic material such
as RNA inhibitor.
Watkin acknowledges that it could be years before the researchers’
work results in diagnostic or treatment methods used in clinical practices.
“We have a lot of potential research directions ahead of us,”
he said. “I think one of the directions this is going to take
is exploring its use at the molecular level with various types of other
high-resolution imaging systems. And if it’s of interest for use
within humans in the end, all of the pharmacological attributes of this
will have to be explored.
"That is, its distribution in the body … where do the nanoparticles
go? What are its effects? How long does it last? All of those kinds
of things are part of the preclinical work, before people can even consider