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MRI is a powerful diagnostic tool for clinical imaging, and many researchers have sought to develop MRI-based strategies that permit the high-resolution, real-time tracking of gene expression in living organisms. Several such techniques have emerged, most of which rely on the use of specially designed metal-complexed contrast compounds for labeling. These compounds, although effective in some cases, generally have drawbacks including poor penetrance into tissues. Carnegie Mellon University researcher Eric Ahrens has worked closely on this problem over the past several years, and sought an alternative solution that bypasses these obstacles.

“I'm very interested in magnetism,” explains Ahrens, “and I became intrigued by these bacteria, magnetotactic bacteria, that make magnetic structures used for navigation.” These unusual organisms migrate along geomagnetic lines with the assistance of magnetosomes, bacterium-produced particles of crystallized magnetic material. “[Magnetosomes are] in many ways similar to superparamagnetic iron oxide particles,” Ahrens continues, “which have gained wide interest for use in cellular imaging... I looked a little further and wondered if there were metalloproteins found in nature that also exhibited properties of superparamagnetism.”

In the end, his group would focus on metalloproteins from the ferritin family, a widely studied class of proteins that are capable of storing iron molecules and have a vital role in regulating iron levels in the body. In a recent article in Nature Medicine, Ahrens' group describes the generation of an adenoviral construct for the constitutive expression of human ferritin. Initial in vitro experiments, wherein cultured cells were infected with the recombinant virus, demonstrated that ferritin was being produced, and that it was capable of effectively sequestering iron present in the culture medium. The resulting increase in iron-loaded ferritin appeared to have no negative impact on cell growth or viability, and allowed the cells to be readily visualized by MRI. Ahrens' group followed up with in vivo tests, injecting the virus into the brains of live mice, and found that within five days they could clearly visualize highly localized regions of strong MRI contrast at the site of injection. This labeling remained distinct even 39 days after injection.

The lab is now refining their system, but Ahrens ultimately sees this approach as a highly adaptable system for the precise in vivo analysis of transgene expression: “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.”