Synthesis and Biological Evaluation of 123I-Labeled Pyridyl Benzoxazole Derivatives: Novel β-Amyloid Imaging Probes for Single-Photon Emission Computed Tomography.
Synthesis and Biological Evaluation of 123I-Labeled Pyridyl Benzoxazole Derivatives: Novel β-Amyloid Imaging Probes for Single-Photon Emission Computed Tomography.
复制标题
123I 标记吡啶基苯并恶唑衍生物的合成和生物学评价：用于单光子发射计算机断层扫描的新型 β-淀粉样蛋白成像探针。
DOI：
10.1039/c4ra10742j
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Saji H.
中科院分区：
文献类型：
--
作者：
Watanabe H;Ono M;Iikuni S;Okamoto Y;Ihara M;Takahashi R;Saji H.
利用正电子发射断层扫描和单光子发射计算机断层扫描等非侵入性技术对β-淀粉样蛋白(A-β)斑块进行体内成像，有助于阿尔茨海默病(AD)的早期诊断和药物发现。在常规诊断方面，SPECT被认为是一种比PET更有用的方法，但在临床研究中还没有关于有吸引力的探针的报道。在本研究中，我们合成并评价了新型~(123)I标记的吡啶基苯并恶唑类化合物作为单光子发射计算机断层扫描探针用于体内A-β斑块的成像。在体外实验中，PBOX衍生物对A-β(1-42)聚集体表现出亲和力(Ki=6.9-138 nm)。在正常小鼠体内的生物分布实验中，所有这些衍生物都表现出较高的初始摄取(2分钟摄取4.6-6.6%ID g−1)和快速清除(60分钟清除0.3-1.3%ID g−1)。此外，在死后AD脑切片的体外放射自显影中，[125I]9清楚地标记了Aβ斑块。[123I]9的SPECT/CT研究显示，Tg2576小鼠的放射性高于野生型小鼠。此外，注射[123I]9后的Tg2576小鼠脑切片的体外放射自显影显示Aβ斑块选择性结合。综上所述，[123I]9可能是一种潜在的AD脑内Aβ斑块的SPECT显像剂。
In vivo imaging of β-amyloid (Aβ) plaques by non-invasive techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) may facilitate early diagnosis and drug discovery for the treatment of Alzheimer's disease (AD). SPECT is known as a more useful modality than PET in terms of routine diagnostic use, but there have been no reports on attractive probes in clinical studies. In this study, we synthesized and evaluated novel 123I-labeled pyridyl benzoxazole (PBOX) derivatives as SPECT probes for imaging Aβ plaques in vivo. The PBOX derivatives showed affinity for Aβ(1–42) aggregates in vitro (Ki = 6.9–138 nM). In biodistibution experiments in normal mice, all these derivatives showed high initial uptake into (4.6–6.6% ID g−1 at 2 min) and rapid clearance (0.3–1.3% ID g−1 at 60 min) from the brain. Furthermore, [125I]9 clearly labeled Aβ plaques in in vitro autoradiography of postmortem AD brain sections. SPECT/CT study with [123I]9 displayed higher radioactivity in Tg2576 mice than wild-type mice. In addition, ex vivo autoradiograms of brain sections from Tg2576 mice after the injection of [123I]9 showed selective binding of Aβ plaques. In conclusion, [123I]9 may be a potential SPECT probe for imaging Aβ plaques in AD brain.