DOI: 10.57760/sciencedb.08488
title: Synthesis and preliminary biological evaluation of a novel PET tracer for α synuclein PET Imaging
title: 新型α突触核蛋白PET探针的合成及初步生物学评价

description: Abstract [Background] Accumulation of α-synuclein is a major hallmark of Parkinson’s disease. The development of PET tracers to visualize aggregated α-synuclein is useful for early diagnosis and treatment of Parkinson's disease.[Purpose] A small molecule compound based on benzothiazole scaffolds, 2-((3-fluorobenzyl)thio)-6-(3-[fluorine-18] propoxy)benzo[d]thiazole ,denoted as 18F-YM,were prepared and labeled using Cu(II) mediated radiofluorination methods respectively. The imaging properties of the tracer were primarily evaluated through PET imaging at A53T mice and normal mice. Also, the imaging properties of the probe was also investigated through biodistribution experiments as well as ex vivo autoradiography and pathological analysis.[Methods] Through chemical synthesis, compounds Sn-YM and 19F-YM were obtained. Compound Sn-YM was labeled with 18F using organic tin fluoride method, and the resulting product 18F-YM was verified by high performance liquid chromatography. 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.
description: Abstract [Background] Accumulation of α-synuclein is a major hallmark of Parkinson’s disease. The development of PET tracers to visualize aggregated α-synuclein is useful for early diagnosis and treatment of Parkinson's disease.[Purpose] A small molecule compound based on benzothiazole scaffolds, 2-((3-fluorobenzyl)thio)-6-(3-[fluorine-18] propoxy)benzo[d]thiazole ,denoted as 18F-YM,were prepared and labeled using Cu(II) mediated radiofluorination methods respectively. The imaging properties of the tracer were primarily evaluated through PET imaging at A53T mice and normal mice. Also, the imaging properties of the probe was also investigated through biodistribution experiments as well as ex vivo autoradiography and pathological analysis.[Methods] Through chemical synthesis, compounds Sn-YM and 19F-YM were obtained. Compound Sn-YM was labeled with 18F using organic tin fluoride method, and the resulting product 18F-YM was verified by high performance liquid chromatography. 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.