Transgenic Mouse (Tg2576) Is an Ideal Model for the Biological Characterization of [18F]-FDDNP for Identifying Alzheimer’s Disease
ABSTRACT
[18F]-FDDNP was synthesized and characterized as a positron-emitting probe to identify Alzheimer’s disease (AD) in transgenic mouse models (Tg2576 and dE9) expressing the AD pathology. We observed in in vitro, in vivo, and ex vivo studies that [18F]-FDDNP accumulated specifically in the Ab-overexpressing brain regions and that this accumulation was significantly reduced by co-incubation with non-radioactive FDDNP. In ex vivo and in vivo studies of brain sections, the retention of radioactivity was more specific in Tg2576 mice than in dE9 mice. Using in vitro, ex vivo, in vivo, and ELISA analyses, we characterized the utility of [18F]-FDDNP in mapping b-amyloid in the Tg2576 mouse brain, to assess its potential application in imaging strategies.
Cite this paper
Chang, K. , Lee, S. and Chen, C. (2015) Transgenic Mouse (Tg2576) Is an Ideal Model for the Biological Characterization of [18F]-FDDNP for Identifying Alzheimer’s Disease. Journal of Biosciences and Medicines, 3, 1-6. doi: 10.4236/jbm.2015.312001.
Chang, K. , Lee, S. and Chen, C. (2015) Transgenic Mouse (Tg2576) Is an Ideal Model for the Biological Characterization of [18F]-FDDNP for Identifying Alzheimer’s Disease. Journal of Biosciences and Medicines, 3, 1-6. doi: 10.4236/jbm.2015.312001.
References
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[1] Newberg, A.B., Wintering, N.A., Pl?ssl, K., Hochold, J., Stabin, M.G., Watson, M., Skovronsky, D., Clark, C.M., Kung, M.P. and Kung, H.F. (2006) Safety, Biodistribution, and Dosimetry of 123I-IMPY: A Novel Amyloid Plaque- Imaging Agent for the Diagnosis of Alzheimer’s Disease. J Nucl Med., 47, 748-754. [2] Reiman, E.M., Uecker, A., Gonzalez-Lima, F., Minear, D., Chen, K., Callaway, N.L., Berndt, J.D. and Games, D. (2000) Tracking Alzheimer’s Disease in Transgenic Mice Using Fluorodeoxyglucose Autoradiography. Neuroreport, 11, 987-991. http://dx.doi.org/10.1097/00001756-200004070-00018 [3] Lee, C.W., Kung, M.P., Hou, C. and Kung, H.F. (2003) Dimethylamino-Fluorenes: Ligands for Detecting β-Amyloid Plaques in the Brain. Nucl Med Biol., 30, 573-580. http://dx.doi.org/10.1016/S0969-8051(03)00050-7 [4] Nakamura, S., Murayama, N., Noshita, T., Annoura, H. and Ohno, T. (2001) Progressive Brain Dysfunction Following Intracerebroventricular Infusion of Beta1-42-Amyloid Pep-tide. Brain Res., 912, 128-136. http://dx.doi.org/10.1016/S0006-8993(01)02704-4 [5] Lockhart, A. (2006) Imaging Alzheimer’s Disease Pathology: One Target, Many Ligands. Drug Discov Today, 11, 1093-1099. http://dx.doi.org/10.1016/j.drudis.2006.10.008 [6] Routtenberg, A. (1997) Measuring Memory in a Mouse Model of Alzheimer’s Disease. Science, 277, 839-841. http://dx.doi.org/10.1126/science.277.5327.839 [7] Barrios, J.R., Kepea, V., Satyamurthy, N., Huang, S.C. and Gary, W. (2006) Brain Pathology and Neuronal Losses in the Living Brain of Alzheimer’s Patients. Int Congr Ser., 1290, 150-155. http://dx.doi.org/10.1016/j.ics.2005.11.102 [8] Giovannelli, L., Casamenti, F., Scali, C., Bartolini, L. and Pepeu, G. (1995) Differential Effects of Amyloid Peptides β-(1-40) and β-(25-35) Injections into the Rat Nucleus Basalis. Neuroscience, 66, 781-792. http://dx.doi.org/10.1016/0306-4522(94)00610-H [9] Liu, J., Kepe, V., Zabjek, A., Petric, A., Padgett, H.C., Satya-murthy, N. and Barrio, J.R. (2007) High-Yield, Automated Radiosynthesis of 2-(1-{6-[(2-[18F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) Ready for Animal or Human Administration. Mol Imaging Biol., 9, 6-16. http://dx.doi.org/10.1007/s11307-006-0061-4 [10] Agdeppa, E.D., Kepe, V., Liu, J., Flores-Torres, S., Satyamurthy, N., Petric, A., Cole, G.M., Small, G.W., Huang, S.C. and Barrio, J.R. (2001) Binding Characteristics of Radiofluorinated 6-Dialkylamino-2-Naphthylethylidene Derivatives as Positron Emission Tomography Imaging Probes for β-Amyloid Plaques in Alzheimer’s Disease. J Neurosci., 21, RC189. [11] Agdeppa, E.D., Kepe, V., Liu, J., Small, G.W., Huang, S.C., Petric, A., Satyamurthy, N. and Barrio, J.R. (2003) 2-Dialkylamino-6-acylmalononitrile Substituted Naphthalenes (DDNP Analogs): Novel Diagnostic and Thera-peutic Tools in Alzheimer’s Disease. Mol Imaging Biol., 5, 404-417. http://dx.doi.org/10.1016/j.mibio.2003.09.010 [12] Kung, H.F., Kung, M.P., Zhuang, Z.P., Hou, C., Lee, C.W., Pl?ssl, K., Zhuang, B., Skovronsky, D.M., Lee, V.M. and Trojanowski, J.Q. (2003) Iodinated Tracers for Imaging Amyloid Plaques in the Brain. Mol Imaging Biol., 5, 418-426. http://dx.doi.org/10.1016/j.mibio.2003.09.003