Visualizing Nerve Injury in a Neuropathic Pain Model with [¹⁸F]FTC-146 PET/MRI.

Area of Science:

• Neuroscience
• Radiochemistry
• Medical Imaging

Background:

• Peripheral nerve injury causes pain and weakness, often difficult to diagnose accurately with current methods.
• Existing imaging techniques lack the specificity and sensitivity for precise diagnosis of nerve injury and associated neuroinflammation.
• The sigma-1 receptor (S1R) is a molecular biomarker implicated in nerve injury and neuropathic pain.

Purpose of the Study:

• To develop and validate a novel imaging strategy for visualizing S1R as a biomarker of nerve injury and neuroinflammation.
• To assess the efficacy of a novel S1R-selective radioligand, [18F]FTC-146, using positron emission tomography-magnetic resonance imaging (PET/MRI).
• To evaluate the potential of S1R-targeted imaging for diagnosis and therapeutic intervention in neuropathic pain.

Main Methods:

• Western blotting to quantify S1R levels in injured versus uninjured nerves in a rat model.
• Development and application of the S1R-selective radioligand [18F]FTC-146 for PET/MRI.
• Ex vivo autoradiography and immunostaining to validate PET/MRI findings.
• Assessment of pain relief through S1R blockade using non-radioactive [19F]FTC-146.

Main Results:

• Western blotting confirmed a two-fold increase in S1Rs in injured nerves.
• [18F]FTC-146 PET/MRI accurately localized the nerve injury site in the rat model.
• Ex vivo analyses showed a strong correlation between [18F]FTC-146 accumulation and S1R staining.
• Local administration of [19F]FTC-146 successfully relieved pain by blocking S1Rs.

Conclusions:

• [18F]FTC-146 PET/MRI is a promising tool for non-invasively visualizing S1R in nerve injury and neuroinflammation.
• This imaging approach offers potential for improved diagnosis and management of patients with peripheral nerve injury.
• Targeting S1R with agents like [19F]FTC-146 may provide a therapeutic strategy for neuropathic pain.