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.
To trigger living cells into producing their own contrast agent, Eric Ahrens, assistant professor of biological sciences in the Mellon College of Science at Carnegie Mellon, 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.
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.
“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,” said Ahrens.
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.