Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
Anat Rec (Hoboken). 2010 Dec;293(12):2136-43. doi: 10.1002/ar.21209.
Amyloid plaques are one of the hallmarks of Alzheimer's disease (AD). The lack of specific probes that can detect individual senile plaques in AD has prompted the development of magnetic resonance imaging (MRI) probes. In this study, based on DTPA-gadolinium (III) and congo red (CR), a novel specific MRI probe precursor CR-BSA-(Gd-DTPA)n was successfully synthesized. Its ability to bind to amyloid plaques was evaluated by brain sections from APP/PS1 transgenic mice. Its specificity for Aβ plaques was further demonstrated by immunohistochemistry (IHC) staining with the monoclonal antibody to the Aβ protein. Meanwhile, the amyloid deposits detected by the CR-BSA-(Gd-DTPA)n were matched to the amyloid deposits detected by Aβ specific antibody. We also found that a few amyloid-like deposits which was not detected by IHC. The findings indicated that the probe perhaps could detect the neurofibrillary tangles (NFT) similar to the effect of CR itself, and this will be verified in future experiments. The works suggested that the Aβ protein-specific magnetic resonance contrast agent precursor CR-BSA-(Gd-DTPA)n can be used as a potential fluorescence and MR multi-modal imaging probe precursor to display individual senile plaques in AD.
淀粉样斑块是阿尔茨海默病(AD)的特征之一。缺乏能够检测 AD 中单个老年斑的特异性探针,促使人们开发了磁共振成像(MRI)探针。在这项研究中,基于 DTPA-钆(III)和刚果红(CR),成功合成了一种新型的特异性 MRI 探针前体 CR-BSA-(Gd-DTPA)n。通过 APP/PS1 转基因小鼠的脑切片评估了其与淀粉样斑块结合的能力。通过用抗 Aβ 蛋白的单克隆抗体进行免疫组织化学(IHC)染色,进一步证明了其对 Aβ 斑块的特异性。同时,CR-BSA-(Gd-DTPA)n 检测到的淀粉样沉积物与 Aβ 特异性抗体检测到的淀粉样沉积物相匹配。我们还发现了一些 IHC 未检测到的类似淀粉样的沉积物。这些发现表明,该探针可能能够检测到类似于 CR 本身的神经纤维缠结(NFT),这将在未来的实验中得到验证。这些工作表明,Aβ 蛋白特异性磁共振对比剂前体 CR-BSA-(Gd-DTPA)n 可用作显示 AD 中单个老年斑的潜在荧光和 MR 多模态成像探针前体。