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Bioorg Med Chem Lett. 2013 Sep 15;23(18):5170-3. doi: 10.1016/j.bmcl.2013.07.014. Epub 2013 Jul 18.

Synthesis and evaluation of a 125I-labeled iminodihydroquinoline-derived tracer for imaging of voltage-gated sodium channels.

Author information

1
Department of Chemistry and Institute of Nuclear Medicine, UCL, London, United Kingdom.

Abstract

In vivo imaging of voltage-gated sodium channels (VGSCs) can potentially provide insights into the activation of neuronal pathways and aid the diagnosis of a number of neurological diseases. The iminodihydroquinoline WIN17317-3 is one of the most potent sodium channel blockers reported to date and binds with high affinity to VGSCs throughout the rat brain. We have synthesized a (125)I-labeled analogue of WIN17317-3 and evaluated the potential of the tracer for imaging of VGSCs with SPECT. Automated patch clamp studies with CHO cells expressing the Nav1.2 isoform and displacement studies with [(3)H]BTX yielded comparable results for the non-radioactive iodinated iminodihydroquinoline and WIN17317-3. However, the (125)I-labeled tracer was rapidly metabolized in vivo, and suffered from low brain uptake and high accumulation of radioactivity in the intestines. The results suggest that iminodihydroquinolines are poorly suited for tracer development.

KEYWORDS:

Imaging; Iodine-125; SPECT; Voltage-gated sodium channel; WIN17317-3

PMID:
23910595
PMCID:
PMC3764405
DOI:
10.1016/j.bmcl.2013.07.014
[Indexed for MEDLINE]
Free PMC Article
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