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Ed. Note: The following
is a press release from Carnegie Mellon University. March 20th, 2005
PITTSBURGH--In a first, Carnegie Mellon University scientists have
"programmed" cells to make their own contrast agents, enabling
unprecedented high-resolution, deep-tissue imaging of gene expression. The
results, appearing in the April issue of Nature Medicine, hold
considerable promise for conducting preclinical studies in the emerging
field of molecular therapeutics and for monitoring the delivery of
therapeutic genes in patients.
"For 20 years it has been the chemist's job to develop agents that can
be used to enhance MRI contrast," said Eric Ahrens, assistant professor of
biological sciences in the Mellon College of Science at Carnegie Mellon.
"Now, with our approach, we have put this job into the hands of the
molecular biologist. Using off-the-shelf molecular biology tools we can
now enable living cells to change their MRI contrast via genetic
instructions."
"The new imaging method is a platform technology that can be adapted
for many tissue types and for a range of preclinical uses in conjunction
with emerging molecular therapeutic strategies," Ahrens said.
Ahrens' new approach uses magnetic resonance imaging (MRI) to monitor
gene expression in real-time. Because MRI images deep tissues
non-invasively and at high resolution, investigators don't need to
sacrifice animals and perform laborious and costly analysis.
To trigger living cells into producing their own contrast agent, Ahrens
gave them a gene that produces a form of ferritin, a protein that normally
stores iron in a non-toxic form. This metalloprotein acts like a nano-magnet
and a potent MRI "reporter."
A typical MRI scan detects and analyzes signals given off by hydrogen
protons in water molecules after they are exposed to a magnetic field and
radiofrequency pulses. These signals are then converted into an image.
Ahrens' new MRI reporter alters the magnetic field in its proximity,
causing nearby protons to give off a distinctly different signal. The
resulting image reveals dark areas that indicate the presence of the MRI
reporter.
"Our technology is adaptable to monitor gene expression in many tissue
types. You could link this MRI reporter gene to any other gene of
interest, including therapeutic genes for diseases like cancer and
arthritis, to detect where and when they are being expressed," Ahrens
said.
Existing methods used to image gene expression have limitations,
according to Ahrens. Some methods cannot be used in living subjects, fail
to image cells deep inside the body or don't provide high-resolution
images. Other approaches using MRI are not practical for a wide range of
applications.
Ahrens and his colleagues constructed a gene carrier, or vector, that
contained a gene for the MRI reporter. They used a widely studied vector
called a replication-defective adenovirus that readily enters cells but
doesn't reproduce itself. Ahrens injected the vector carrying the MRI
reporter gene into brains of living mice and imaged the MRI reporter
expression periodically for over a month in the same cohort of animals.
The research showed no overt toxicity in the mouse brain from the MRI
reporter.
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Ahrens consulted on aspects of the research with William Goins, a
research assistant professor at the University of Pittsburgh. The work was
funded by the Pittsburgh Life Sciences Greenhouse and the National
Institute of Biomedical Imaging and Bioengineering.
Ahrens is a member of the Pittsburgh NMR Center for Biomedical
Research, a joint endeavor sponsored by Carnegie Mellon University and the
University of Pittsburgh. Established in 1986 and funded continuously
since 1988 by the National Institutes of Health, the Pittsburgh NMR Center
is dedicated to advancing molecular, cellular and functional imaging in
animals.
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