Magnetic resonance imaging of amyloid plaques using hollow manganese oxide nanoparticles conjugated with antibody ab1–40 in a transgenic mouse model Jae-Hun Kim a , Tae Lin Ha c , Geun Ho Im d , Jehoon Yang d , Sang Won Seo b , In Su Lee e and Jung Hee Lee a,d In this study, we have shown the feasibility of hollow manganese oxide nanoparticles (HMON) conjugated with an antibody of Ab1–40 peptide (abAb40) (HMON-abAb40) for MRI of amyloid plaques in APP/PS1 transgenic mice. MR brain images in APP/PS1 transgenic mice and their nontransgenic littermates were acquired using a 7.0 T MRI system before, and 24 and 72 h after an injection of HMON-abAb40. After the injection of HMON-abAb40, we found hyperenhanced spots in the frontal cortex area on T1-weighted MR images for transgenic mice, which corresponded qualitatively to amyloid plaques detected by thioflavin-S staining. For quantitative analysis, percent MR signal changes in six brain regions (olfactory cortex, frontal cortex, cerebral cortex, thalamus, hippocampus, and cerebellar cortex) were compared between transgenic and wild-type mice. We found significant increases in the percent MR signal changes in the olfactory cortex, frontal cortex, cerebral cortex, and hippocampus, but there were no significant differences in the thalamus and cerebellar cortex for transgenic mice compared with wild-type mice. This unique strategy allowed us to detect brain regions subjected to amyloid plaque deposition in Alzheimer’s disease transgenic mouse models and has a potential to be developed for human applications, which has a current utility in preclinical research, particularly in monitoring therapeutic response for drug development in Alzheimer’s disease. NeuroReport 24:16–21  c 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. NeuroReport 2013, 24:16–21 Keywords: Alzheimer’s disease, amyloid plaque, hollow manganese oxide nanoparticles, magnetic resonance imaging Departments of a Radiology, b Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, c Department of Applied Chemistry, Kyung Hee University, d Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute, Seoul and e Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, Korea Correspondence to Jung Hee Lee, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea Tel: + 82 23 410 6459; fax: + 82 23 410 0084; e-mail: hijunghee@skku.edu Received 23 September 2012 accepted 17 October 2012 Introduction Alzheimer’s disease is the most common cause of dementia, which is pathologically characterized by amyloid plaques and neurofibrillary tangles [1]. There is a prevailing concept that an imbalance between the produc- tion and clearance of amyloid b (Ab) is the initiating event in the pathogenesis of Alzheimer’s disease [2]. According to the amyloid cascade hypothesis, it initially causes the aggregation of Ab, leading to amyloid plaques that may progress to pathological events including the formation of neurofibrillary tangles, cortical atrophy, and dementia. Along with rapid developments of technologies for molecular imaging, researchers have attempted to develop a method for imaging amyloid plaques in vivo over the last decade. PET technology using 11 C-PIB (Pittsburgh compound B) has been used for the detection of amyloid plaques in patients with Alzheimer’s disease [3–5]. However, PIB-PET imaging has several limitations in the detection of individual amyloid plaques: a low spatial resolution without an anatomical background, the short half-life of the radio- active ligand, and a general radiation problem. In addition, there is a deficiency for high-affinity binding of PIB to detect Ab deposits, which limits the use in transgenic mice [6,7]. Owing to the favorable safety and easy accessibility of MRI techniques along with the high spatial resolution anatomical images it provides, researchers have continuously attempted to develop MRI techniques to detect amyloid plaques in vivo [8–17]. High-resolution T2-weighted or T2*-weighted MRI has been applied for the noninva- sive detection of amyloid plaques on the basis of the speculation that amyloid plaques contain iron deposits [8–11]. However, intrinsic T2 or T2* contrast arising from iron often fails to distinguish iron in the plaques from those in blood vessels or hemorrhages. Furthermore, these techniques only allow the detection of iron- containing plaques on the basis of the content of the plaque, not the size of the plaque [11]. Several groups have developed molecular imaging tech- niques to visualize amyloid plaques in MRI using contrast agents that are conjugated with amyloid plaque-targeting ligands [14–17]. Gadolinium-diethylenetriaminepenta- acetic acid, monocrystalline iron oxide nanoparticles, or ultrasmall superparamagnetic iron oxide nanoparticles conjugated with a fragment of the Ab peptide were applied to image amyloid plaques with the aid of mannitol or putrescine to open up the blood–brain barrier (BBB) [14–17]. Their results showed that hyperen- 16 Brain imaging 0959-4965  c 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/WNR.0b013e32835ba850 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.