title: [F-18]FDDNP microPET imaging correlates with brain Aβ burden in a transgenic rat model of Alzheimer disease: effects of aging, in vivo blockade, and anti-Aβ antibody treatment.
abstract: In vivo detection of Alzheimer's disease (AD) neuropathology in living patients using positron emission tomography (PET) in conjunction with high affinity molecular imaging probes for β-amyloid (Aβ) and tau has the potential to assist with early diagnosis, evaluation of disease progression, and assessment of therapeutic interventions. Animal models of AD are valuable for exploring the in vivo binding of these probes, particularly their selectivity for specific neuropathologies, but prior PET experiments in transgenic mice have yielded conflicting results. In this work, we utilized microPET imaging in a transgenic rat model of brain Aβ deposition to assess [F-18]FDDNP binding profiles in relation to age-associated accumulation of neuropathology. Cross-sectional and longitudinal imaging demonstrated that [F-18]FDDNP binding in the hippocampus and frontal cortex progressively increases from 9 to 18months of age and parallels age-associated Aβ accumulation. Specificity of in vivo [F-18]FDDNP binding was assessed by naproxen pretreatment, which reversibly blocked [F-18]FDDNP binding to Aβ aggregrates. Both [F-18]FDDNP microPET imaging and neuropathological analyses revealed decreased Aβ burden after intracranial anti-Aβ antibody administration. The combination of this non-invasive imaging method and robust animal model of brain Aβ accumulation allows for future longitudinal in vivo assessments of potential therapeutics for AD that target Aβ production, aggregation, and/or clearance. These results corroborate previous analyses of [F-18]FDDNP PET imaging in clinical populations.
authors: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. eteng@ucla.edu
authors: Edmond
authors: E
authors: Teng
authors: Vladimir
authors: V
authors: Kepe
authors: Sally A
authors: SA
authors: Frautschy
authors: Jie
authors: J
authors: Liu
authors: Nagichettiar
authors: N
authors: Satyamurthy
authors: Fusheng
authors: F
authors: Yang
authors: Ping-Ping
authors: PP
authors: Chen
authors: Graham B
authors: GB
authors: Cole
authors: Mychica R
authors: MR
authors: Jones
authors: Sung-Cheng
authors: SC
authors: Huang
authors: Dorothy G
authors: DG
authors: Flood
authors: Stephen P
authors: SP
authors: Trusko
authors: Gary W
authors: GW
authors: Small
authors: Gregory M
authors: GM
authors: Cole
authors: Jorge R
authors: JR
authors: Barrio
references: Lancet Neurol. 2008 Feb;7(2):129-35
references: 18191617
references: J Neurosci. 2001 Dec 15;21(24):RC189
references: 11734604
references: Mol Imaging Biol. 2009 Mar-Apr;11(2):100-6
references: 18679755
references: J Cereb Blood Flow Metab. 1989 Dec;9(6):830-9
references: 2531146
references: CNS Neurol Disord Drug Targets. 2010 Apr;9(2):140-8
references: 20205646
references: J Nucl Med. 2009 Feb;50(2):191-7
references: 19164243
references: J Neurosci. 2000 Aug 1;20(15):5709-14
references: 10908610
references: J Neurosci. 2003 May 1;23(9):3745-51
references: 12736345
references: Neurobiol Aging. 2010 Oct;31(10):1669-78
references: 19004525
references: Acta Neuropathol. 1991;82(4):239-59
references: 1759558
references: Mol Imaging Biol. 2007 Jan-Feb;9(1):6-16
references: 17051324
references: Brain. 2008 Jun;131(Pt 6):1630-45
references: 18339640
references: J Neuropathol Exp Neurol. 2008 Jan;67(1):30-40
references: 18091561
references: J Nucl Med. 2010 Jun;51(6):913-20
references: 20501908
references: Mol Imaging Biol. 2009 Jul-Aug;11(4):236-40
references: 19214638
references: J Neurosci. 2007 Oct 10;27(41):10957-68
references: 17928437
references: Am J Geriatr Psychiatry. 2002 Jan-Feb;10(1):24-35
references: 11790632
references: Am J Pathol. 2004 Sep;165(3):987-95
references: 15331422
references: J Nucl Med. 2005 Mar;46(3):455-63
references: 15750159
references: Phys Med Biol. 2005 Apr 21;50(8):1837-50
references: 15815099
references: J Biol Chem. 2001 Apr 20;276(16):12991-8
references: 11152675
references: Ann Neurol. 2010 Sep;68(3):319-29
references: 20687209
references: Nucl Med Biol. 2008 Nov;35(8):869-74
references: 19026948
references: Mol Imaging Biol. 2009 Sep-Oct;11(5):322-33
references: 19340487
references: Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6222-7
references: 20304798
references: Neuroscience. 2003;117(3):723-30
references: 12617976
references: Biochemistry. 2002 Jan 22;41(3):922-8
references: 11790115
references: Neurobiol Dis. 2008 Jul;31(1):46-57
references: 18504134
references: J Neurol Neurosurg Psychiatry. 2010 Aug;81(8):882-4
references: 20543188
references: Neuroimage. 2010 Jan 1;49(1):240-8
references: 19703569
references: Proc Natl Acad Sci U S A. 1985 Jun;82(11):3863-7
references: 3873656
references: Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17459-60
references: 20921385
references: N Engl J Med. 2006 Dec 21;355(25):2652-63
references: 17182990
references: Brain. 2009 May;132(Pt 5):1355-65
references: 19339253
references: Mol Imaging. 2003 Jul;2(3):131-7
references: 14649056
references: J Nucl Med. 2004 Sep;45(9):1431-4
references: 15347707
references: Arch Neurol. 2007 Mar;64(3):431-4
references: 17353389
references: Neuron. 2004 Aug 5;43(3):321-32
references: 15294141
references: Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4501-6
references: 19246392
references: Neurology. 2007 May 15;68(20):1718-25
references: 17502554
references: Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2256-66
references: 18604533
references: J Neurosci. 2005 Nov 16;25(46):10598-606
references: 16291932
references: Am J Geriatr Psychiatry. 2004 Nov-Dec;12(6):584-95
references: 15545326
references: Arch Neurol. 2009 Dec;66(12):1557-62
references: 20008664
references: J Neurosci. 2001 Nov 1;21(21):8370-7
references: 11606625
references: Lancet Neurol. 2010 Apr;9(4):363-72
references: 20189881
references: Phys Med Biol. 2006 Jan 21;51(2):379-90
references: 16394345
references: Neuron. 2004 Sep 2;43(5):633-45
references: 15339646
references: Brain Res Bull. 1995;38(1):77-85
references: 7552378
references: J Biol Chem. 2005 Feb 18;280(7):5892-901
references: 15590663
references: Neurobiol Aging. 2009 Jul;30(7):1078-90
references: 18053619
references: Eur J Nucl Med Mol Imaging. 2005 May;32(5):593-600
references: 15791432
references: Ann Neurol. 2004 Mar;55(3):306-19
references: 14991808