by Pérez-Medina, Carlos, Patel, Niral, Robson, Mathew, Lythgoe, Mark F and Arstad, Erik
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.
Reference:
Synthesis and evaluation of a 125I-labeled iminodihydroquinoline-derived tracer for imaging of voltage-gated sodium channels. (Pérez-Medina, Carlos, Patel, Niral, Robson, Mathew, Lythgoe, Mark F and Arstad, Erik), In Bioorganic & medicinal chemistry letters, volume 23, 2013.
Bibtex Entry:
@article{PerezMedina:2013eg,
author = {P{'e}rez-Medina, Carlos and Patel, Niral and Robson, Mathew and Lythgoe, Mark F and Arstad, Erik},
title = {{Synthesis and evaluation of a 125I-labeled iminodihydroquinoline-derived tracer for imaging of voltage-gated sodium channels.}},
journal = {Bioorganic {&} medicinal chemistry letters},
year = {2013},
volume = {23},
number = {18},
pages = {5170--5173},
month = sep,
affiliation = {Department of Chemistry and Institute of Nuclear Medicine, UCL, London, United Kingdom.},
doi = {10.1016/j.bmcl.2013.07.014},
pmid = {23910595},
pmcid = {PMC3764405},
language = {English},
rating = {0},
date-added = {2013-11-24T10:34:45GMT},
date-modified = {2020-07-09T13:27:49GMT},
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.},
url = {http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=23910595&retmode=ref&cmd=prlinks},
uri = {url{papers3://publication/doi/10.1016/j.bmcl.2013.07.014}}
}