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
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Two α-synuclein ligands, 3-methoxy-7-nitro-10H
= 32.1 ± 1.3 nM) and 3-(2-fluoroethoxy)-7-nitro-10H
= 49.0 ± 4.9 nM), were radiolabeled as potential PET imaging agents by respectively introducing 11
C and 18
F. The syntheses of [11
were accomplished in a good yield with high specific activity. Ex vivo
biodistribution studies in rats revealed that both [11
crossed the blood-brain barrier (BBB) and demonstrated good brain uptake 5 min post-injection. MicroPET imaging of [11
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 [11
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).