Synthesis and preliminary biological evaluation of a novel PET tracer for α synuclein PET Imaging

The in vitro stability and octanol–water partition coefficient of 18F-YM were determined. Finally, small animal Micro PET imaging was used to assess the affinity of 18F-YM for α-synuclein, and autoradiography, pathological analysis, and biodistribution were used to validate the results of small animal Micro PET imaging.[Results] 18F labeled small molecule compound was prepared in nearly 1 hour and obtained with an undecayed yield greater than 10% and the radiochemical purity was greater than 95%.

In vivo PET imaging revealed that more radioactivity was significantly detected in the brain of A53T mice than those of normal mice after administration of 18F-YM. Quantitative analysis showed that the uptake values in the brain of A53T mice and normal mice were 2.35±0.06 %ID/g and 1.38±0.15 %ID/g.Furthermore, ex vivo autoradiography and histological examination confirmed the possibility of detection of aggregated α-synuclein in thalamus, substantia nigra and striatum using 18F-YM.

A biodistribution study in normal mice found that 18F- YM was quickly cleaned from the brain of normal mice. It indicates that the non-specific binding of 18F- YM in the brain is low, which allowed for obtaining good contrast images. [Conclusion] The preclinical study demonstrated that the benzothiazole analog，18F- YM，owned preferable imaging prosperities.

It may be a new candidate for α-synuclein PET imaging.