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

Pérez-Medina, C; Patel, N; Robson, M; Lythgoe, MF; Arstad, E; (2013) Synthesis and evaluation of a (125)I-labeled iminodihydroquinoline-derived tracer for imaging of voltage-gated sodium channels. Bioorganic & Medicinal Chemistry Letters , 23 (18) pp. 5170-5173. 10.1016/j.bmcl.2013.07.014. Green open access

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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.

Type: Article
Title: Synthesis and evaluation of a (125)I-labeled iminodihydroquinoline-derived tracer for imaging of voltage-gated sodium channels
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bmcl.2013.07.014
Publisher version: http://dx.doi.org/10.1016/j.bmcl.2013.07.014
Language: English
Additional information: © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
Keywords: Imaging, Iodine-125, SPECT, Voltage-gated sodium channel, WIN17317-3
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1404995
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