title: Radiosynthesis andin VivoEvaluation of Two PET Radioligands for Imaging α-Synuclein.
abstract: Two α-synuclein ligands, 3-methoxy-7-nitro-10H-phenothiazine (2a,Ki= 32.1 ± 1.3 nM) and 3-(2-fluoroethoxy)-7-nitro-10H-phenothiazine (2b,Ki= 49.0 ± 4.9 nM), were radiolabeled as potential PET imaging agents by respectively introducing11C and18F. The syntheses of [11C]2aand [18F]2bwere accomplished in a good yield with high specific activity.Ex vivobiodistribution studies in rats revealed that both [11C]2aand [18F]2bcrossed the blood-brain barrier (BBB) and demonstrated good brain uptake 5 min post-injection. MicroPET imaging of [11C]2ain a non-human primate (NHP) confirmed that the tracer was able to cross the BBB with rapid washout kinetics from brain regions of a healthy macaque. The initial studies suggested that further structural optimization of [11C]2aand [18F]2bis necessary in order to identify a highly specific positron emission tomography (PET) radioligand forin vivoimaging of α-synuclein aggregation in the central nervous system (CNS).
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors: Xiang
authors: X
authors: Zhang
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors: Hongjun
authors: H
authors: Jin
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors: Prashanth K
authors: PK
authors: Padakanti
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors: Junfeng
authors: J
authors: Li
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors: Hao
authors: H
authors: Yang
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors: Jinda
authors: J
authors: Fan
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors: Robert H
authors: RH
authors: Mach
authors: Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, USA.
authors: Paul
authors: P
authors: Kotzbauer
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors: Zhude
authors: Z
authors: Tu
keywords: Lewy bodies; PET; Parkinson's disease; phenothiazine; radiosynthesis; α-synuclein
references: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11282-6
references: 8248242
references: Neurology. 2012 Mar 6;78(10 ):696-701
references: 22323748
references: Neuron. 1995 Aug;15(2):361-72
references: 7646890
references: Neurology. 2000 May 23;54(10):1916-21
references: 10822429
references: Bioorg Med Chem. 2011 Mar 1;19(5):1666-73
references: 21315609
references: Bioorg Med Chem Lett. 2012 Aug 1;22(15):5104-7
references: 22749281
references: Arch Phys Med Rehabil. 2005 Feb;86(2):183-9
references: 15706541
references: Trends Neurosci. 1998 Jun;21(6):249-54
references: 9641537
references: Mov Disord. 2008 Apr 30;23(6):837-44
references: 18307261
references: Neuron. 2006 Oct 5;52(1):33-8
references: 17015225
references: J Neurosci. 2007 Feb 7;27(6):1405-10
references: 17287515
references: Mol Neurodegener. 2010 Dec 07;5:55
references: 21138585
references: J Chem Neuroanat. 2011 Dec;42(4):242-8
references: 21167933
references: J Neurochem. 2008 Apr;105(1):78-90
references: 17988241
references: Arch Neurol. 2008 Dec;65(12):1577-81
references: 19064744
references: Neurology. 2012 Mar 6;78(10 ):688-9
references: 22323757
references: J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):368-76
references: 18344392
references: Bioorg Med Chem. 2012 Aug 1;20(15):4625-34
references: 22789706
references: PLoS One. 2013;8(2):e55031
references: 23405108
references: Nucl Med Biol. 2010 May;37(4):509-16
references: 20447563
references: J Nucl Med. 1999 Jan;40(1):205-12
references: 9935078
references: Geriatr Gerontol Int. 2010 Jul;10 Suppl 1:S180-96
references: 20590833