Radiosynthesis and in vivo evaluation of two PET radioligands for imaging α-synuclein

Xiang Zhang; Hongjun Jin; Prashanth K. Padakanti; Junfeng Li; Hao Yang; Jinda Fan; Robert H. Mach; Paul Kotzbauer; Zhude Tu

doi:10.3390/app4010066

Radiosynthesis and in vivo evaluation of two PET radioligands for imaging α-synuclein

Xiang Zhang, Hongjun Jin, Prashanth K. Padakanti, Junfeng Li, Hao Yang, Jinda Fan, Robert H. Mach, Paul Kotzbauer, Zhude Tu

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

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 introducing ¹¹C and ¹⁸F. The syntheses of [¹¹C]2a and [¹⁸F]2b were accomplished in a good yield with high specific activity. Ex vivo biodistribution studies in rats revealed that both [¹¹C]2a and [¹⁸F]2b crossed the blood-brain barrier (BBB) and demonstrated good brain uptake 5 min post-injection. MicroPET imaging of [¹¹C]2a in 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]2a and [¹⁸F]2b is necessary in order to identify a highly specific positron emission tomography (PET) radioligand for in vivo imaging of α-synuclein aggregation in the central nervous system (CNS).

Original language	English
Pages (from-to)	66-78
Number of pages	13
Journal	Applied Sciences (Switzerland)
Volume	4
Issue number	1
DOIs	https://doi.org/10.3390/app4010066
State	Published - Mar 1 2014

Keywords

Lewy bodies
PET
Parkinson's disease
Phenothiazine
Radiosynthesis
α-synuclein

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title = "Radiosynthesis and in vivo evaluation 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 introducing 11C and 18F. The syntheses of [11C]2a and [18F]2b were accomplished in a good yield with high specific activity. Ex vivo biodistribution studies in rats revealed that both [11C]2a and [18F]2b crossed the blood-brain barrier (BBB) and demonstrated good brain uptake 5 min post-injection. MicroPET imaging of [11C]2a in 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]2a and [18F]2b is necessary in order to identify a highly specific positron emission tomography (PET) radioligand for in vivo imaging of α-synuclein aggregation in the central nervous system (CNS).",

keywords = "Lewy bodies, PET, Parkinson's disease, Phenothiazine, Radiosynthesis, α-synuclein",

author = "Xiang Zhang and Hongjun Jin and Padakanti, {Prashanth K.} and Junfeng Li and Hao Yang and Jinda Fan and Mach, {Robert H.} and Paul Kotzbauer and Zhude Tu",

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AU - Zhang, Xiang

AU - Jin, Hongjun

AU - Padakanti, Prashanth K.

AU - Li, Junfeng

AU - Yang, Hao

AU - Fan, Jinda

AU - Mach, Robert H.

AU - Kotzbauer, Paul

AU - Tu, Zhude

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AB - 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 introducing 11C and 18F. The syntheses of [11C]2a and [18F]2b were accomplished in a good yield with high specific activity. Ex vivo biodistribution studies in rats revealed that both [11C]2a and [18F]2b crossed the blood-brain barrier (BBB) and demonstrated good brain uptake 5 min post-injection. MicroPET imaging of [11C]2a in 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]2a and [18F]2b is necessary in order to identify a highly specific positron emission tomography (PET) radioligand for in vivo imaging of α-synuclein aggregation in the central nervous system (CNS).

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Radiosynthesis and in vivo evaluation of two PET radioligands for imaging α-synuclein

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