MRI Technique for Gene Mapping

A new study demonstrates that an iron-storage molecule in the cell can function as a sophisticated tool for mapping gene expression. Gene therapy in the near future may utilize a method in which noninvasive magnetic resonance imaging (MRI) is used to monitor this molecule.

The study was conducted in the biologic regulation department of the Weizmann Institute of Science (Rehovot, Israel). The investigators developed the ability of the iron-bearing ferritin molecule to be utilized as a kind of a gene "spy” by engineering genetic adaptations to cells. This approach made ferritin sensitive to tetracycline (TET), a traditional antibiotic, so that when TET is present, the ferritin is inactivated and when TET is absent, ferritin in activated. Tumor cells with modified ferritin were inserted into living mice and then tracked with MRI scanning. The scientists suppressed the expression of ferritin in the inserted cells by administering TET to the mice. When they stopping giving TET, the ferritin was "turned on,” triggering ferritin molecules to increase their numbers, thus causing an increase in iron uptake within the tumor cells. The difference between the iron content in these and in the healthy surrounding cells was visualized on the MRI scans (which are sensitive to magnetic particles such as iron), accurately detecting the genetically engineered cells.

The advantage of this noninvasive method is that cells are visible using MRI without the need for an additional contrast agent. This technique has significant potential for tracking the progress of gene therapy, including that used to reactivate the body's manufacturing of insulin in the treatment of diabetes, because these genes can be "tagged” before injecting. Therapeutic genes can then be monitored by MRI scanning to make sure the target is reached and the desired activations occur.

"The use of ferritin as a reporter gene would be particularly beneficial in those cases where administration of contrast material is compromised by barriers, including embryonic development and the central nervous system,” said Prof. Michal Neeman, from the Weizmann Institute, lead author of the study. The study's findings were published in the February 2005 issue of the journal Neoplasia.