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Theranostics 2017; 7(11):2794-2805. doi:10.7150/thno.19378 This issue Cite

Research Paper

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

Bin Shen^1†, Deepak Behera^1†, Michelle L. James^1†, Samantha T. Reyes¹, Lauren Andrews¹, Peter W. Cipriano¹, Michael Klukinov², Amanda Brosius Lutz³, Timur Mavlyutov⁴, Jarrett Rosenberg ¹, Arnold E. Ruoho⁴, Christopher R. McCurdy⁵, Sanjiv S. Gambhir^{1, 6}, David C. Yeomans², Sandip Biswal^1✉, Frederick T. Chin^1✉

1. Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA;
2. Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA;
3. Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA;
4. Department of Neuroscience, University of Wisconsin, Madison, WI 53726, USA;
5. Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA;
6. Departments of Bioengineering and Materials Sciences & Engineering, Stanford University, Stanford, CA 94305, USA.
^† Authors contributed equally

✉ Corresponding author: Dr. Frederick T. Chin, Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, 1201 Welch Road, Rm PS049, Stanford, CA 94305-5484 USA. Tel: +1-(650) 725-4182. e-mail address: chinfedu. Dr. Sandip Biswal, Division of Musculoskeletal Radiology, Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive S-068B, Stanford, CA 94305 USA. Tel: +1-(650) 725-8018. Email address: biswaledu. More

Abstract

The ability to locate nerve injury and ensuing neuroinflammation would have tremendous clinical value for improving both the diagnosis and subsequent management of patients suffering from pain, weakness, and other neurologic phenomena associated with peripheral nerve injury. Although several non-invasive techniques exist for assessing the clinical manifestations and morphological aspects of nerve injury, they often fail to provide accurate diagnoses due to limited specificity and/or sensitivity. Herein, we describe a new imaging strategy for visualizing a molecular biomarker of nerve injury/neuroinflammation, i.e., the sigma-1 receptor (S1R), in a rat model of nerve injury and neuropathic pain. The two-fold higher increase of S1Rs was shown in the injured compared to the uninjured nerve by Western blotting analyses. With our novel S1R-selective radioligand, [¹⁸F]FTC-146 (6-(3-[¹⁸F]fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one), and positron emission tomography-magnetic resonance imaging (PET/MRI), we could accurately locate the site of nerve injury created in the rat model. We verified the accuracy of this technique by ex vivo autoradiography and immunostaining, which demonstrated a strong correlation between accumulation of [¹⁸F]FTC-146 and S1R staining. Finally, pain relief could also be achieved by blocking S1Rs in the neuroma with local administration of non-radioactive [¹⁹F]FTC-146. In summary, [¹⁸F]FTC-146 S1R PET/MR imaging has the potential to impact how we diagnose, manage and treat patients with nerve injury, and thus warrants further investigation.

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