B World Molecular Imaging Society, 2012 Published Online: 26 June 2012 DOI: 10.1007/s11307-012-0567-x Mol Imaging Biol (2013) 15:48Y57 RESEARCH ARTICLE In Vivo Magnetic Resonance Imaging of Transgenic Mice Expressing Human Ferritin Hoe Suk Kim, 1,2 Hyun Jung Joo, 1,3 Ji Su Woo, 1 Yoon Seok Choi, 1,3 Seung Hong Choi, 1 Hyeonjin Kim, 1 Woo Kyung Moon 1,2,3 1 Department of Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul, 110-744, Korea 2 The Institute of Radiation Medicine, Medical Research Center, Seoul National University, 101 Daehangno, Jongno-gu, Seoul, 110-744, Korea 3 Department of Biomedical Science, College of Medicine, Seoul National University, Seoul, 101 Daehangno, Jongno-gu, Seoul, 110-744, Korea Abstract Objective: This study aims to produce the transgenic mice (TG) engineered for magnetic resonance imaging (MRI) studies based on the ubiquitous expression of ferritin MRI reporter gene in diverse tissues. Procedures: Transgenic mice (TG) expressing myc-tagged human heavy chain ferritin (myc-hFTH) under the control of a ubiquitous CAG promoter were produced. The expression of myc-hFTH in diverse tissues of the myc-hFTH TG was assessed by RT-PCR, Western blotting, and immunohis- tochemistry. The iron accumulation and the deposition of ferritin aggregates in tissues of myc-hFTH TG and WT were analyzed by Prussian blue staining and transmission electron microscopy. The myc- hFTH TG (n 0 9) and wild-type mice (WT) (n0 4) were subjected to MRI on 9.4 T MR scanner. An eight- point T 2 * mapping was performed using a multiple gradient echo sequence, and T 2 * value was estimated pixel by pixel by using a routine least-squares fitting algorithm. Results: We generated the myc-hFTH TG expressing myc-hFTH in brain, heart, liver, lung, spleen, pancreas, kidney, and intestine. The myc-hFTH TG showed no apparent pathological symptoms and no histological changes compared to WT. The expression of myc-hFTH in the brain and liver tissues of myc-hFTH TG led to a significant decrease in T 2 * values, as shown by noninvasive MRI, compared to WT (P G 0.05, TG vs. WT). Conclusions: This study demonstrates that the novel myc-hFTH TG, which expresses an MRI reporter in many tissues, would be a valuable animal model of FTH-based molecular imaging in which to study potential therapies for cell and tissue grafting using an MRI technique. These mice could also serve to study disease related with iron metabolism. Key Words: Ferritin, Transgenic mouse, Magnetic resonance imaging, Molecular imaging, MR reporter Introduction F erritin is a compound essential to life. Also known as the iron storage protein, ferritin was recently suggested to be a candidate reporter for the detection of gene expression by magnetic resonance imaging (MRI) [1–3]. The ferritin heavy polypeptide subunit (FTH) has a potent ferroxidase activity that catalyzes the oxidation of ferrous iron. In particular, FTH showing a high transverse relaxation rate at very low iron loading on the magnetic field has been demonstrated as a reproducible and functional MR reporter on extensive molecular imaging studies [4–8]. TET-mFTH transgenic mice (TG) that overexpress mouse FTH (mFTH) and green fluorescent protein (GFP) in a tetracycline inducible manner were previously reported [9]. Hoe Suk Kim and Hyun Jung Joo contributed equally to this work. Correspondence to: Woo Kyung Moon; e-mail: moonwk@snu.ac.kr