posted on 2022-01-12, 14:33authored byHiroyuki Watanabe, Rinka Maekawa, Shimpei Iikuni, Masashi Kakae, Nagisa Matsuo, Hisashi Shirakawa, Shuji Kaneko, Masahiro Ono
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-PODP-DM 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.