准确量化淀粉样蛋白（Aβ）斑块是阿尔茨海默病诊断和治疗的重要指标。为此，通过调节氮原子的位置和数量设计出了新的高灵敏度Aβ示踪剂。合成了一系列含有不同数量和位置N原子的florbetapir（AV45）衍生物，并对其进行了体外亲和力和体内生物分布的评估。初步研究结果显示，[18F] BIBD-124和[18F] BIBD-127在ICR（癌症研究所）小鼠中的清除率和生物分布程度比AV45更好。放射自显影和分子对接显示，[18F] BIBD-124 / 127的结合位点与[18F] AV45类似。微小正电子发射断层扫描成像进一步证明[18F] BIBD-124可以监测Aβ斑块，类似于[18F] AV45，且其成像对比度更好。质谱代谢分析显示，BIBD-124的去甲基化程度比AV45低，没有后续的乙酰化，这可能解释其更少的非特异性摄取和更高的成像对比度。高斯计算进一步证实了在[18F] BIBD-124中引入N5可以减少去甲基化。考虑到成像对比度和体内除氟反应，[18F] BIBD-124有望成为进一步临床试验的有前途的Aβ斑块示踪剂。

Accurate quantification of amyloid beta (Aβ) plaques is an important indicator for Alzheimer's disease diagnosis and treatment. For this purpose, new highly sensitive Aβ tracers were designed by regulating the position and number of nitrogen atoms. A series of derivatives of florbetapir (AV45) containing different numbers and positions of N atoms were synthesized and evaluated for in vitro affinity and in vivo biodistribution. Preliminary study results showed that [18F]BIBD-124 and [18F]BIBD-127 had better clearance rates and less in vivo defluorination than AV45 in ICR (ICR = Institute of Cancer Research) mice. Autoradiography and molecular docking indicated that the binding sites of [18F]BIBD-124/127 were similar to that of [18F]AV45. Micro-positron emission tomography-computed tomography imaging further demonstrated that [18F]BIBD-124 could monitor Aβ plaques similar to [18F]AV45. Besides, the imaging contrast of [18F]BIBD-124 is better than that of [18F]AV45. Mass spectrometric metabolic analysis showed that BIBD-124 was less demethylated than AV45 without subsequent acetylation, which might explain its less non-specific uptake and higher imaging contrast. Gauss calculations further confirmed that the introduction of N5 in [18F]BIBD-124 decreased demethylation. Considering imaging contrast and in vivo defluorination, [18F]BIBD-124 is expected to be a promising radiotracer of Aβ plaques for further clinical trials.