4.6 Article

Characterization of Radioiodinated Diaryl Oxadiazole Derivatives as SPECT Probes for Detection of Myelin in Multiple Sclerosis

期刊

ACS CHEMICAL NEUROSCIENCE
卷 13, 期 3, 页码 363-369

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.1c00753

关键词

myelin; multiple sclerosis; SPECT; imaging

资金

  1. JSPS KAKENHI [17H05092, 20H03622]
  2. Grants-in-Aid for Scientific Research [20H03622, 17H05092] Funding Source: KAKEN

向作者/读者索取更多资源

This study characterized four diaryl oxadiazole derivatives as potential myelin-imaging probes for single photon emission computed tomography (SPECT) in multiple sclerosis (MS). The results showed that one of the derivatives, [123I]1,3,4-PODP-DM, could potentially be used as a SPECT probe for imaging myelin in MS.
Multiple sclerosis (MS) is an intractable disease of the central nervous system that results from destruction of the myelin sheath. Direct measurement of de- and remyelination is required for monitoring the disease stage of MS, but no useful method has been established. In this study, we characterized four diaryl oxadiazole derivatives as novel myelin-imaging probes for single photon emission computed tomography (SPECT). All the diaryl oxadiazole derivatives penetrated the blood-brain barrier in normal mice. Among them, the highest ratio of radioactivity accumulation in the white matter (myelin-rich region) against the gray matter (myelin-deficient region) was observed at 60 min postinjection of [125I]1,3,4-PODP-DM in ex vivo autoradiography using normal mice. In the blocking study with ex vivo autoradiography, the radioactivity accumulation of [125I]1,3,4-PODP-DM in the white matter markedly reduced. [125I]1,3,4-PODPDM detected demyelination in the ex vivo autoradiographic images of not only the spinal cord of the experimental autoimmune encephalomyelitis mice but also the brain after lysophosphatidylcholine (LPC) injection. In addition, [123I]1,3,4-PODP-DM could image LPC-induced demyelination in the mouse brain with SPECT. These results suggest that [123I]1,3,4-PODP-DM may be a potential SPECT probe for imaging myelin in MS.

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