Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Bioorg Med Chem. 2011 May 1;19(9):2980-90. doi: 10.1016/j.bmc.2011.03.029. Epub 2011 Mar 21.
To develop agents for radionuclide imaging Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (K(i)=5.5nM) and the specific binding to Aβ in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in radiolabeled form as an Aβ plaques-specific positron emission tomography (PET) imaging probe, we investigated synthetic route suitable for its labeling with the short-lived PET radionuclide fluorine-18 (t(1/2)=110min) and diaryliodonium tosylate precursors (12, 13a-e and 14). 2-Aryl-6-[(18)F]fluorobenzothiazoles ([(18)F]1-3) were synthesized in efficiently short reaction times (40-60min) with high radiochemical yields (19-40%), purities (>95%) and specific activities (85-118GBq/μmol). Tissue distribution studies showed that high radioactivity of [(18)F]2 accumulated in the brain with rapid clearance in healthy mice. Radioactive metabolites were analyzed in brain samples of mice and corresponded to 81% of parent remained by 30min after a tail-vein injection. These results suggest that [(18)F]2 is a promising probe for evaluation of Aβ plaques imaging in brain using PET.
为了开发用于体内放射性核素成像 Aβ 斑块的试剂，我们制备了三种芳基苯并噻唑类的氟取代类似物；化合物 2 对 Aβ 具有高亲和力（K(i)=5.5nM），并且在荧光染色中对 Aβ 的特异性结合。为了合成这些芳基苯并噻唑类似物的放射性标记形式，作为 Aβ 斑块特异性正电子发射断层扫描（PET）成像探针，我们研究了适合用短寿命 PET 放射性核素氟-18（t(1/2)=110min）和二芳基碘鎓对甲苯磺酸盐前体（12、13a-e 和 14）标记的合成路线。2-芳基-6-[[18]F]氟苯并噻唑([(18)F]1-3)在高效短反应时间（40-60min）内以高放射化学产率（19-40%）、纯度（>95%）和比活度（85-118GBq/μmol）合成。组织分布研究表明，健康小鼠脑中[（18）F]2的放射性高，清除迅速。在尾静脉注射后 30min 内，用放射性代谢物分析小鼠脑组织，发现放射性母体的 81%仍存在。这些结果表明，[（18）F]2是一种很有前途的探针，可用于使用 PET 评估脑内 Aβ 斑块的成像。
