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Targeting α7-Nicotinic Acetylcholine Receptor Expression to Noninvasively Image and Localize Peripheral Nerve Injuries
Arman T. Zadeh
*, Fares Lebbos, Zachary Zamore, Jeffrey Khong, Rachana Suresh, Christopher Erb, Jared Zhang, William Padovano, Ala Elhelali, Sami Tuffaha
Plastic Surgery, Johns Hopkins University, Baltimore, MD
BACKGROUNDPeripheral nerve injuries (PNIs) cause significant disability and affect ~67,800 individuals annually in the U.S. Timely identification and localization are critical to surgical reconstruction. Current diagnostic modalities, such as electrodiagnostic studies and magnetic resonance imaging (MRI), provide incomplete and potentially misleading information, hindering optimal management. We identified the α7-Nicotinic Acetylcholine Receptor (α7-nAChR), a neuroinflammatory modulator on macrophages and Schwann cells, as a potential biomarker of PNIs. We hypothesized that the FDA-approved PET radiotracer [18F]ASEM, which targets α7-nAChR, could detect and localize nerve injury in a rat sciatic nerve injury model.
METHODS27 male Lewis rats underwent right sciatic nerve transection without repair, followed by ex vivo biodistribution at 1 week. Rats received intravenous [18F]ASEM and were harvested at 5-180 minutes post-injection (n=4-5/timepoint). Tissues included proximal and distal injured nerve, contralateral nerve, bilateral muscle, blood, brain, and kidney. Uptake was quantified as % injected dose per gram (%ID/g). A second cohort (n=10) underwent transection with immediate repair (n=5) or no repair (n=5) and was evaluated at 3 weeks. Two additional rats underwent dynamic PET/MRI at 1 week.
RESULTSAt 180 minutes, [18F]ASEM uptake was significantly higher in distal injured nerve compared to healthy nerve and muscle (p=0.006). At 3 weeks, uptake remained elevated in unrepaired nerves versus contralateral controls (p<0.01) and was reduced in repaired nerves, suggesting sensitivity to injury state and recovery. Dynamic PET/MRI demonstrated focal tracer accumulation at injury sites with high spatial resolution.
CONCLUSIONSPET imaging with [18F]ASEM enables noninvasive detection and localization of PNI in a rat model. Uptake reflects the expected spatial and temporal profile of degeneration and is modulated by repair. These findings support further translation of α7-nAChR as an imaging biomarker of PNI to guide diagnosis, surgical planning, and monitoring in PNIs.
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