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; Parkinson’s disease; PET; phenothiazine; radiosynthesis; α-synuclein
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Zhang, X.; Jin, H.; Padakanti, P.K.; Li, J.; Yang, H.; Fan, J.; Mach, R.H.; Kotzbauer, P.; Tu, Z. Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein. Appl. Sci. 2014, 4, 66-78.
Zhang X, Jin H, Padakanti PK, Li J, Yang H, Fan J, Mach RH, Kotzbauer P, Tu Z. Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein. Applied Sciences. 2014; 4(1):66-78.
Zhang, Xiang; Jin, Hongjun; Padakanti, Prashanth K.; Li, Junfeng; Yang, Hao; Fan, Jinda; Mach, Robert H.; Kotzbauer, Paul; Tu, Zhude. 2014. "Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging α-Synuclein." Appl. Sci. 4, no. 1: 66-78.