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-10
H-phenothiazine (
2a,
Ki = 32.1 ± 1.3 nM) and 3-(2-fluoroethoxy)-7-nitro-10
H-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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