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A 18F‑Labeled Saxitoxin Derivative for in Vivo PET-MR Imaging of Voltage-Gated Sodium Channel Expression Following Nerve Injury
journal contribution
posted on 2013-12-04, 00:00 authored by Aileen Hoehne, Deepak Behera, William H. Parsons, Michelle
L. James, Bin Shen, Preeti Borgohain, Deepika Bodapati, Archana Prabhakar, Sanjiv
S. Gambhir, David C. Yeomans, Sandip Biswal, Frederick T. Chin, J. Du BoisBoth chronic and neuropathic pain
conditions are associated with
increased expression of certain voltage-gated sodium ion channel (NaV) isoforms in peripheral sensory neurons. A method for noninvasive
imaging of these channels could represent a powerful tool for investigating
aberrant expression of NaV and its role in pain pathogenesis.
Herein, we describe the synthesis and evaluation of a positron emission
tomography (PET) radiotracer targeting NaVs, the design
of which is based on the potent, NaV-selective inhibitor
saxitoxin. Both autoradiography analysis of sciatic nerves excised
from injured rats as well as whole animal PET-MR imaging demonstrate
that a systemically administered [18F]-labeled saxitoxin
derivative concentrates at the site of nerve injury, consistent with
upregulated sodium channel expression following axotomy. This type
of PET agent has potential use for serial monitoring of channel expression
levels at injured nerves throughout wound healing and/or following
drug treatment. Such information may be correlated with pain behavioral
analyses to help shed light on the complex molecular processes that
underlie pain sensation.