School of Pharmacy, Bengbu Medical College, Anhui, Bengbu 233030, China; Department of Nuclear Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, Hefei 230001, China.
Department of Nuclear Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, Hefei 230001, China.
Bioorg Med Chem. 2022 Dec 1;75:117087. doi: 10.1016/j.bmc.2022.117087. Epub 2022 Nov 5.
[F]BAY-94-9172, [F]AV-45, and [F]GE-067 were FDA approved positron emission tomography (PET) imaging radiotracer of β-amyloid plaques (Aβ) in Alzheimer's disease (AD). However, the radiochemical synthesis requires multi-step reactions and complex procedure. Recently, a protocol for radiochemical synthesis of sulfur fluoride exchange (SuFEx) using ultrafast F/F isotopic exchange had been reported. We developed three pairs of novel F-labeled radiotracers by the "SuFEx" method for PET imaging Aβ plaques. The F labeling reaction can be completed quickly (30 s) at room temperature and purified using solid-phase extraction (SPE). The radiochemical purity (RCP) of the products was all greater than 95 %. In vitro fluorescent staining using Aβ-transgenesis mice section preliminary verified the affinity of tracers with Aβ. Competitive binding assay displayed high affinity of tracers for towards artificial Aβ aggregates (K values ranging from 3.53 ± 0.39 to 42.0 ± 4.24 nM). In vivo biodistribution and Micro-PET imaging showed that [F]-Sulfur Fluoride β-Amyloid ([F]SFA 1-6) could penetration the blood-brain barrier (BBB) in wild-type mice, and [F]SFA 5-6 had a high initial brain uptake value (3.65 ± 0.9 % and 5.07 ± 0.1 % ID/g, respectively) and a fast washout (Brain uptake = 4.15 and 4.61, respectively) from the brain. In vitro autoradiography demonstrated the affinity of the [F]SFA 5-6 to Aβ plaques in AD human brain tissues. Our results suggested that [F]SFA maybe a potential PET radiotracers for detecting Aβ in Alzheimer's disease.
[F]BAY-94-9172、[F]AV-45 和 [F]GE-067 是美国食品和药物管理局（FDA）批准的用于阿尔茨海默病（AD）β-淀粉样斑块（Aβ）的正电子发射断层扫描（PET）成像放射性示踪剂。然而，放射化学合成需要多步反应和复杂的程序。最近，一种使用超快 F/F 同位素交换的硫氟交换（SuFEx）放射性化学合成的方案已经报道。我们通过“SuFEx”方法开发了三对新型 F 标记的放射性示踪剂，用于 PET 成像 Aβ斑块。F 标记反应可以在室温下快速（30s）完成，并通过固相萃取（SPE）进行纯化。产物的放射化学纯度（RCP）均大于 95%。使用 Aβ 转基因小鼠切片进行体外荧光染色初步验证了示踪剂与 Aβ的亲和力。竞争结合实验显示，示踪剂对人工 Aβ聚集体具有高亲和力（K 值范围为 3.53±0.39 至 42.0±4.24nM）。体内生物分布和 Micro-PET 成像显示，[F]-硫氟化物β-淀粉样蛋白（[F]SFA 1-6）可以穿透野生型小鼠的血脑屏障（BBB），[F]SFA 5-6 具有较高的初始脑摄取值（分别为 3.65±0.9%和 5.07±0.1%ID/g）和快速洗脱（脑摄取分别为 4.15 和 4.61）。体外放射自显影显示了 [F]SFA 5-6 与 AD 人脑组织中 Aβ斑块的亲和力。我们的结果表明，[F]SFA 可能是一种用于检测阿尔茨海默病中 Aβ的潜在 PET 放射性示踪剂。
