Advanced Review Ferritin nanoparticles as magnetic resonance reporter gene Batya Cohen, 1 Keren Ziv, 1 Vicki Plaks, 1 Alon Harmelin 1 and Michal Neeman ∗ Dynamic imaging of gene expression in live animals is among the exciting challenges of molecular imaging. To achieve that, one of the approaches is to use reporter genes that encode for the synthesis of easily detectable products. Such reporter genes can be designed to be expressed under the control of the regulatory elements included in a promoter region of a gene of interest, thus allowing the use of the same reporter gene for the detection of multiple genes. The most commonly used reporter genes include the firefly light-generating enzyme luciferase and the green fluorescent protein detectable by bioluminescence and fluorescence optical imaging, respectively. Over the last years a number of studies demonstrated the ability to use the iron-binding protein ferritin as a reporter gene that allows the detection of gene expression by magnetic resonance imaging (MRI). MRI provides high spatial resolution and soft tissue contrast for deep tissues along with a large arsenal of functional and anatomical contrast mechanisms that can be correlated with gene expression, and can potentially be translated into clinical use.  2009 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2009 1 181–188 O ne of the important challenges for the new field of molecular imaging is to develop the tools that would provide noninvasive dynamic information on transcriptional regulation of gene expression. Such information would aid not only biological and preclinical research but could possibly assist in the guidance of gene therapy and in detecting and monitoring of the fate of cells during treatment. A popular approach is to utilize reporter genes that can be detected noninvasively by imaging. Thus, the promoters of the genes of interest are used for inducing the expression of reporter gene coding for easily detectable proteins. To serve as a reporter, it is important to show not only that it can be detected in a manner that would faithfully correlate spatially and temporally with transcriptional regulation, but also that its expression in the cells of interest will not alter the fate of the cells. The review presented here describes the use of ferritin, an iron-binding natural nanoparticle as an endogenous magnetic resonance imaging (MRI) reporter gene. ∗ Correspondence to: Michal Neeman, Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. E-mail: michal.neeman@weizmann.ac.il 1 Weizmann Institute of Science, Rehovot 76100, Israel DOI: 10.1002/wnan.011 PATHOLOGIES OF IRON HOMEOSTASIS Iron, a major trace element, is both toxic and essential for life. Iron is an integral component of many proteins such as cytochromes, hemoglobin, and myoglobin and is critical for their activity. However, free iron catalyzes radical formation in oxygenated tissues (Fenton’s reaction) leading to cell damage. The balance between iron storage and utilization is maintained by regulation of intestinal absorption of the metal from the diet, along with the expression of iron transport and storage proteins including transferrin, transferrin receptor, hepcidin, and ferritin. 1 Both iron deficiency as well as iron overload lead to diverse pathological changes, which are among the most prevalent human diseases. 2 Iron deficiency, characterized by smaller red blood cells and low transferrin saturation, can arise in rapidly growing children and premenopausal women in whom iron demand exceeds dietary supply, 3 as well as in blood loss associated with tumors, inflammation, infections, inherited defects in iron metabolism, and autoimmune diseases. Anemia of chronic disease is attributed frequently to the inability to release iron from macrophages or loading of transferrin. The result is a normochromic, normocytic anemia in which total Volume 1, March/April 2009  2009 John Wiley & Sons, Inc. 181