Synthesis and bioactivity evaluation of a myelin-specific contrast agent for magnetic resonance imaging of myelination in central nervous system

Bin Wei; Na Weng; Lei Fu; Yuxuan Li; Xu Wang; Ruijuan Yin; Tao Jiang

doi:10.1016/j.bmc.2023.117257

Synthesis and bioactivity evaluation of a myelin-specific contrast agent for magnetic resonance imaging of myelination in central nervous system

Bioorg Med Chem. 2023 Apr 15:84:117257. doi: 10.1016/j.bmc.2023.117257. Epub 2023 Mar 21.

Authors

Bin Wei¹, Na Weng², Lei Fu¹, Yuxuan Li¹, Xu Wang³, Ruijuan Yin⁴, Tao Jiang⁵

Affiliations

¹ Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
² Department of Nuclear Medicine, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China.
³ Department of Nuclear Medicine, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China. Electronic address: wangxu1978@163.com.
⁴ Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Marine Biomedical Research Institute of Qiangdao, Ocean University of China, Qingdao, 266237, China. Electronic address: yinruijuan@ouc.edu.cn.
⁵ Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.

PMID: 37001243
DOI: 10.1016/j.bmc.2023.117257

Abstract

Demyelination exists in many neurological diseases of nervous system, such as stroke. Currently, magnetic resonance imaging (MRI) has been the main tool for diagnosing and monitoring the myelin related diseases. However, the conventional MRI unable to distinguish demyelinating lesions from other inflammatory lesions. To address this problem, we have designed and prepared a myelin specific magnetic resonance contrast agent, Gd-DTDAS, which was based myelin specific moiety MeDAS^g and Gd-DTPA^h. In this work, we verified the specificity and sensitivity of Gd-DTDAS to myelin. Moreover, we investigated the specific binding ability of Gd-DTDAS to myelin sheath in the MCAO miceⁱ models. The in vivo imaging results showed that Gd-DTDAS can bind to the undamaged myelin sheath in the BBB disruption areas, and in turn reduce the relaxation time. The fluorescence images also showed significant fluorescence in the brain right infarct area of the MCAO model mice with administration of Gd-DTDAS. The above results confirmed that Gd-DTDAS could be preferentially distributed in areas with high myelination and can detect focally induced demyelination.

Keywords: Gd-DTPA; MRI; Myelination; Specificity; Stroke.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Central Nervous System / diagnostic imaging
Central Nervous System / metabolism
Contrast Media*
Demyelinating Diseases* / metabolism
Magnetic Resonance Imaging / methods
Mice
Myelin Sheath / metabolism

Substances

Contrast Media