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

Research Paper

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

Bin Shen1†, Deepak Behera1†, Michelle L. James1†, 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. Gambhir1, 6, David C. Yeomans2, Sandip Biswal1✉, Frederick T. Chin1✉

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, University of Mississippi, University, MS 38677, USA;
6. Departments of Bioengineering and Materials Sciences & Engineering, Stanford University, Stanford, CA 94305, USA.
Authors contributed equally

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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How to cite this article:
Shen B, Behera D, James ML, Reyes ST, Andrews L, Cipriano PW, Klukinov M, Lutz AB, Mavlyutov T, Rosenberg J, Ruoho AE, McCurdy CR, Gambhir SS, Yeomans DC, Biswal S, Chin FT. Visualizing Nerve Injury in a Neuropathic Pain Model with [18F]FTC-146 PET/MRI. Theranostics 2017; 7(11):2794-2805. doi:10.7150/thno.19378. Available from http://www.thno.org/v07p2794.htm