Neuroinflammation at the Neuroforamina and Spinal Cord in Patients with Painful Cervical Radiculopathy and Pain-Free Participants: An [11C]DPA713 PET/CT Proof-of-Concept Study

Abstract

Background/Objectives: The complex pathophysiology of painful cervical radiculopathy is only partially understood. Neuroimmune activation in the dorsal root ganglion and spinal cord is assumed to underlie the genesis of radicular pain. Molecular positron emission tomography (PET) using the radiotracer [¹¹C]DPA713, which targets the 18-kDa translocator protein (TSPO), offers the ability to quantify neuroinflammation in humans in vivo. The primary objectives of this study were to (1) assess whether uptake of [¹¹C]DPA713, a metric of neuroinflammation, is higher in the neuroforamina and spinal cord of patients with painful cervical radiculopathy compared with that in pain-free participants and (2) assess whether [¹¹C]DPA713 uptake is associated with clinical parameters, such as pain intensity. Methods: Dynamic 60 min [¹¹C]DPA713 PET/CT scans were acquired, and regions of interest were defined for neuroforamina and spinal cord. Resulting time-activity curves were fitted to a single-tissue compartment model using an image-derived input function, corrected for plasma-to-whole blood ratios and parent fractions, to obtain the volume of distribution (V_T) as the primary outcome measure. Secondary neuroinflammation metrics included 1T2k V_T without metabolite correction (1T2k_WB) and Logan V_T. Results: The results indicated elevated levels of 1T2k V_T at the neuroforamina (p < 0.04) but not at the spinal cord (p = 0.16). Neuroforamina and spinal cord 1T2k V_T lack associations with clinical parameters. Secondary neuroinflammatory metrics show associations with clinical parameters such as the likelihood of neuropathic pain. Conclusions: These findings enhance our understanding of painful cervical radiculopathy's pathophysiology, emphasizing the neuroforamina levels of neuroinflammation as a potential therapeutic target.

Keywords: PET imaging; cervical radiculopathy; immunoactivation; neuroinflammation; neuropathic pain.

Figure 1

Neuroinflammation in a patient with a C6 right painful cervical radiculopathy and a pain-free participant. To quantify [¹¹C]DPA713 binding at the neuroforamina and spinal cord, we utilized an image-derived input single tissue compartmental (1T2k) model. For visualization purposes, we generated volume of distribution (V_T) images using Logan plot analysis, with a time threshold of t* = 30. (A): T1-weighted MRI of the patient with a painful cervical radiculopathy. The dotted line indicates the cross-sectional area used for the CT and PET analysis. (B): Parametric cross-sectional image of [¹¹C]DPA713 binding merged with CT, with a zoomed view at the neuroforamina (NF) and spinal cord (SC). Higher volume of distribution (V_T) indicates more tracer binding, suggesting higher levels of neuroinflammation. (C): T1-weighted MRI of a pain-free participant. (D): Follow-up parametric cross-sectional image of [¹¹C]DPA713 binding merged with CT, with a zoomed view at the neuroforamina (NF) and spinal cord (SC).

Figure 2

Heatmap showing the association (standardized-β) between non-linearized and linearized (semi-)quantification of [¹¹C]DPA713 binding at the neuroforamina and spinal cord with clinical parameters in patients with cervical radiculopathy. * represents an association with a p-value below 0.05. No post-hoc comparisons were made. Associations were determined with genotype as a confounding factor. Abbreviations: 1T2k: single tissue compartmental model; 1T2k_WB: 1T2k without metabolite correction; BMI: Body Mass Index; hsCRP: high sensitive c-reactive protein; VAS: visual analogue scale; CSI: likelihood of central sensitization; painDETECT: likelihood of neuropathic pain; CROM-PAIN: Pain intensity at maximal cervical rotation Scale; CROM: maximal cervical rotation; PPT: Pressure Pain Threshold.