A 18F-Labeled Saxitoxin Derivative for in Vivo PET-MR Imaging of Voltage-Gated Sodium Channel Expression Following Nerve Injury

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• 作者：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 Bois
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：December 4, 2013
• 年：2013
• 卷：135
• 期：48
• 页码：18012-18015
• 全文大小：289K
• 年卷期：v.135,no.48(December 4, 2013)
• ISSN：1520-5126

文摘

Both chronic and neuropathic pain conditions are associated with increased expression of certain voltage-gated sodium ion channel (Na_V) isoforms in peripheral sensory neurons. A method for noninvasive imaging of these channels could represent a powerful tool for investigating aberrant expression of Na_V and its role in pain pathogenesis. Herein, we describe the synthesis and evaluation of a positron emission tomography (PET) radiotracer targeting Na_Vs, the design of which is based on the potent, Na_V-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.