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."
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.
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.
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."
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
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
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.
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
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.
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.