Neeman, together with Dr. Batya Cohen of the Institute's Molecular Genetics Department, developed the capacity of the iron-bearing ferritin molecule to serve as a sort of gene "spy" by making genetic modifications to cells. This approach rendered ferritin sensitive to tetracycline (TET), a common antibiotic, so that when TET is present, the ferritin is "off" and when TET is absent, ferritin is "on." Tumor cells with modified ferritin were inserted into living mice and then tracked with MRI. The researchers hampered the expression of ferritin in the inserted cells through the administration of TET. When they stopped the TET, the "switch" turned on, triggering ferritin molecules to increase their numbers, thereby causing an increase in iron uptake within the tumor cells. The contrast between the iron content in these and in the normal surrounding cells showed up in the MRI (which is sensitive to magnetic particles such as iron), effectively identifying the genetically modified cells.
This method grew out of a joint vision that originated 10 years ago in collaboration with the late Dr. Yoav Citri. Ferritin's advantage is that it is visible in MRI without the need for an additional contrast material. This technique has far-reaching implications for monitoring the progress of gene therapy, such as that used to reactivate the body's production of insulin in the treatment of diabetes, because the genes can be "tagged" prior to injection. Therapeutic genes can then be tracked by MRI to ensure the target is reached and the desired activations occur. Prof. Neeman: "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."
Prof. Michal Neeman's research is supported by the M.D. Moross Institute for Cancer Research; the Willner Family Center for Vascular Biology; the Women's Health Research Center; the Mark Family Foundation; and Mr. and Mrs. Stephen Meadow, Beverly Hills, CA.
Journal
Neoplasia