To develop novel norepinephrine transporter (NET)-targeting positron emission tomography (PET) probes with optimal pharmacokinetic properties, a series of meta-bromobenzylguanidine derivatives was synthesized. 4-Fluorodiethoxyethane-3-bromobenzylguanidine (compound 12) showed relatively good affinity for the NET (IC₅₀ = 1.00 ± 0.04 μM). The corresponding radiotracer ¹⁸F-12 was prepared in high radiochemical purity (>98%) via a three-step method. The in vitro cellular uptake results demonstrated that ¹⁸F-12 was specifically taken up by NET-expressing SK-N-SH cells by the uptake-1 mechanism. Biodistribution studies in mice showed that ¹⁸F-12 exhibited high cardiac uptake (10.45 ± 0.66 %ID/g at 5 min p.i. and 6.44 ± 0.40 %ID/g at 120 min p.i.), faster liver clearance, and a lower dose of absorbed radiation than [¹²³I]-labeled meta-iodobenzylguanidine ([¹²³I]MIBG). Small animal PET imaging confirmed the high heart-to-background ratio of ¹⁸F-12 and the uptake-1 mechanism specific for the NET in rats, indicating its potential as a promising PET radiotracer for cardiac sympathetic nerve imaging.

中文翻译：

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新型 [18F]-标记间溴苄基胍衍生物：用于去甲肾上腺素转运体的潜在正电子发射断层扫描成像探针

为了开发具有最佳药代动力学特性的新型去甲肾上腺素转运蛋白 (NET) 靶向正电子发射断层扫描 (PET) 探针，合成了一系列间溴苄基胍衍生物。4-氟二乙氧基乙烷-3-溴苄基胍（化合物12）对 NET 表现出较好的亲和力（IC ₅₀ = 1.00 ± 0.04 μM）。通过三步法以高放射化学纯度 (>98%) 制备相应的放射性示踪剂¹⁸ F-12 。体外细胞摄取结果表明¹⁸ F-12通过摄取 1 机制被表达 NET 的 SK-N-SH 细胞特异性摄取。小鼠体内的生物分布研究表明，¹⁸ F-12与 [ ¹²³ I] 标记的 meta-碘苄基胍（[ ¹²³ I]MIBG）。^{小动物 PET 成像证实了18} F-12的高心脏与背景比和大鼠 NET 特有的摄取 1 机制，表明其作为心脏交感神经成像的有前途的 PET 放射性示踪剂的潜力。