title: A 18F-labeled saxitoxin derivative for in vivo PET-MR imaging of voltage-gated sodium channel expression following nerve injury.
abstract: Both 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 [(18)F]-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.
authors.affiliation: Department of Radiology, ‡Department of Chemistry, and §Department of Anesthesia, Stanford University , Stanford, California 94305, United States.
authors.forename: Aileen
authors.initials: A
authors.lastname: Hoehne
authors.forename: Deepak
authors.initials: D
authors.lastname: Behera
authors.forename: William H
authors.initials: WH
authors.lastname: Parsons
authors.forename: Michelle L
authors.initials: ML
authors.lastname: James
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.forename: Preeti
authors.initials: P
authors.lastname: Borgohain
authors.forename: Deepika
authors.initials: D
authors.lastname: Bodapati
authors.forename: Archana
authors.initials: A
authors.lastname: Prabhakar
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: David C
authors.initials: DC
authors.lastname: Yeomans
authors.forename: Sandip
authors.initials: S
authors.lastname: Biswal
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
authors.forename: J
authors.initials: J
authors.lastname: Du Bois
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D009437:Neuralgia / Q000175:diagnosis* / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D012530:Saxitoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism; D061567:Voltage-Gated Sodium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry*; D061566:Voltage-Gated Sodium Channels / Q000032:analysis* / Q000378:metabolism
chemical_list: D005462:Fluorine Radioisotopes; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D012530:Saxitoxin