Discovery of 1,2,3-Triazole Derivatives for Multimodality PET/CT/Cryoimaging of Myelination in the Central Nervous System

Myelin pathology is present in many
neurological conditions such
as multiple sclerosis (MS) and traumatic spinal cord injury (SCI).
To facilitate development of novel therapies aimed at myelin repair,
we set out to develop imaging agents that permit direct quantification
of myelination in vivo. In this work, we designed and synthesized
a series of fluorescent fluorinated myelin imaging agents that can
be used for in vivo positron emission tomography (PET) imaging combined
with subsequent post-mortem fluorescent cryoimaging. Structure–activity
relationship (SAR) studies of the newly developed myelin imaging agents
led us to identify a lead compound (TAFDAS, 21) that
readily enters the brain and spinal cord and selectively binds to
myelin. By conducting sequential PET and 3D cryoimaging in an SCI
rat model, we demonstrated for the first time that PET and cryoimaging
can be combined as a novel technique to image the spinal cord with
high sensitivity and spatial resolution.