Vithanarachchi Sashiprabha M, Foley Casey D, Trimpin Sarah, Ewing James R, Ali Meser M, Allen Matthew J
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, 48202, MI, USA.
Department of Chemistry, University of Colombo, Colombo 03, Sri Lanka.
Contrast Media Mol Imaging. 2016 Nov;11(6):492-505. doi: 10.1002/cmmi.1711. Epub 2016 Sep 6.
Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin-specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin-specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results. Here, we describe the synthesis and application of multimodal myelin-specific imaging agents for light microscopy and magnetic resonance imaging. The imaging agents were synthesized by incorporating the structural features of luxol fast blue MBS, a myelin-specific histological stain, into texaphyrins coordinated to Gd . These new complexes demonstrated absorption of visible light, emission of near-IR light, and relaxivity values greater than clinically approved contrast agents for magnetic resonance imaging. These properties enable the use of optical imaging and magnetic resonance imaging for visualization of myelin. We performed section- and en block-staining of ex vivo mouse brains to investigate the specificity for myelin of the new compounds. Images obtained from light microscopy and magnetic resonance imaging demonstrate that our complexes are retained in white matter structures and enable detection of myelin. Copyright © 2016 John Wiley & Sons, Ltd.
可靠的髓鞘成像方法对于研究脱髓鞘的病因以及促进髓鞘再生的药物至关重要。髓鞘特异性化合物可被开发成成像探针，通过各种成像技术来检测髓鞘。多模态髓鞘特异性成像探针的开发使得能够使用正交成像技术准确地可视化髓鞘含量并验证实验结果。在此，我们描述了用于光学显微镜和磁共振成像的多模态髓鞘特异性成像剂的合成与应用。这些成像剂是通过将髓鞘特异性组织学染色剂卢戈氏快蓝MBS的结构特征并入与钆配位的 texaphyrins 中而合成的。这些新的配合物表现出可见光吸收、近红外光发射以及弛豫率值高于临床上批准用于磁共振成像的造影剂。这些特性使得能够利用光学成像和磁共振成像来可视化髓鞘。我们对离体小鼠脑进行了切片和整块染色，以研究新化合物对髓鞘的特异性。从光学显微镜和磁共振成像获得的图像表明，我们的配合物保留在白质结构中并能够检测到髓鞘。版权所有© 2016 约翰威立父子有限公司。
