阿尔茨海默症（Alzheimer’s Disease, AD），是一种神经元退行性疾病，临床表现为认知功能障碍、记忆力衰退及生活自理能力减退，最终导致死亡。脑内β-淀粉样斑块沉积是AD的主要病理特征之一。目前，用于PET显像的Aβ斑块分子探针已经趋于成熟，但SPECT类Aβ斑块显像剂至今并未取得突破性进展。基于我国和大多数发展中国家中SPECT的普及程度明显高于PET的基本国情和99mTc优良的核素性质，研究99mTc标记的Aβ斑块分子探针具有重要的实际应用价值和社会意义。 本文以2-芳基苯并噻唑为先导化合物，bis(aminoethanethiol) (BAT)为鳌合基团，通过悬挂法设计合成一类99mTc标记的Ab斑块分子探针，并制备了相应的稳定铼化合物。体外荧光染色实验表明，4个铼配体均能与AD转基因小鼠脑内的Aβ斑块特异性结合且本底较低。体外竞争结合实验显示铼配体13d与合成的Aβ1-42聚集体具有高亲和性（Ki = 8.46 ± 3.88 nM）。正常小鼠体内生物分布实验结果表明，[99mTc]13a-d均具有较高的初始脑摄取，其中，[99mTc]13d的初始脑摄取最高，达到1.74%ID/g。此外，[99mTc]13d的脑清除速率较快，2min/60 min摄取比高达7.25，且血本底较低（3.97%ID/g）。可见，[99mTc]13d有望发展成为用于SPECT显像的Aβ斑块分子探针。

Alzheimer’s disease (AD) is a neurodegenerative disorder, and it is characterized by the devastating loss of memory and cognitive abilities, and total disability. The β-amyloid plaques in the brain represent a defining pathologic feature of AD. At present, the imaging of Aβ plaques in vivo with positron emission tomography (PET) has achieved remarkable progress, while the development of single photon emission computed tomography (SPECT) tracers lags far behind. However, among the nuclear imaging techniques in China and most developing countries, SPECT is more popular than PET. Thus, the study of 99mTc-labeled molecular imaging probes targeting Aβ plaques is crucial and meaningful. Four novel 99mTc/Re complexes were synthesized by coupling bis(aminoethanethiol) (BAT) chelating ligand via a propoxy-spacer to phenyl or pyridyl benzothiazole, and they were biologically evaluated as potential SPECT probes for imaging Aβ plaques in AD brain. In vitro fluorescent staining indicated that the corresponding rhenium complexes selectively stained the Aβ plaques in sections of brain tissue from transgenic mice. The Re complex 13d showed high affinity for Aβ(1−42) aggregates (Ki = 8.46 ± 3.88 nM). Biodistribution experiments in normal mice revealed that the 99mTc-labeled derivatives displayed sufficient uptake in the brain (0.61-1.74%ID/g at 2 min post-injection). Notably, [99mTc]13d showed a high initial brain uptake (1.74% ID/g at 2 min) and a fast washout from the brain (0.24% ID/g at 60 min), the brain2 min /60 min ratio is 7.25. The preliminary results indicate that [99mTc]13d may be a potential SPECT probe for imaging Aβ plaques in Alzheimer’s brains.