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. 2022 Dec 23;12(1):116.
doi: 10.3390/jcm12010116.

Evaluation of (R)-[11C]PK11195 PET/MRI for Spinal Cord-Related Neuropathic Pain in Patients with Cervical Spinal Disorders

Makoto Kitade  1 , Hideaki Nakajima  1 , Tetsuya Tsujikawa  2 , Sakon Noriki  3 , Tetsuya Mori  4 , Yasushi Kiyono  4 , Hidehiko Okazawa  4 , Akihiko Matsumine  1
Affiliations

Evaluation of (R)-[11C]PK11195 PET/MRI for Spinal Cord-Related Neuropathic Pain in Patients with Cervical Spinal Disorders

Makoto Kitade et al. J Clin Med. .

Abstract

Activated microglia are involved in secondary injury after acute spinal cord injury (SCI) and in development of spinal cord-related neuropathic pain (NeP). The aim of the study was to assess expression of translocator protein 18 kDa (TSPO) as an indicator of microglial activation and to investigate visualization of the dynamics of activated microglia in the injured spinal cord using PET imaging with (R)-[11C]PK11195, a specific ligand for TSPO. In SCI chimeric animal models, TSPO was expressed mainly in activated microglia. Accumulation of (R)-[3H]PK11195 was confirmed in autoradiography and its dynamics in the injured spinal cord were visualized by (R)-[11C]PK11195 PET imaging in the acute phase after SCI. In clinical application of (R)-[11C]PK11195 PET/MRI of the cervical spinal cord in patients with NeP related to cervical disorders, uptake was found in cases up to 10 months after injury or surgery. No uptake could be visualized in the injured spinal cord in patients with chronic NeP at more than 1 year after injury or surgery, regardless of the degree of NeP. However, a positive correlation was found between standardized uptake value ratio and the severity of NeP, suggesting the potential of clinical application for objective evaluation of chronic NeP.

Keywords: [11C]PK11195 PET/MRI; activated microglia; neuropathic pain; spinal cord; spinal disorders; translocator protein 18 kDa (TSPO).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Colocalization of cell-specific markers (NeuN for neurons, CD11b for microglia/macrophages, CC1 for oligodendrocytes and GFAP for astrocytes) and translocator protein 18 kDa (TSPO) in the injured spinal cord at 4 days after spinal cord injury. Most TSPO merged with CD11b, a marker of activated microglia and/or macrophages. TSPO did not colocalize with markers for neurons, oligodendrocytes, and astrocytes. Scale bars = 20 μm.
Figure 2
Figure 2
Immunofluorescent staining showing GFP-positive/TSPO-positive and GFP-negative/TSPO-positive cells at the injured site at 1, 4, 7, 14 and 28 days after SCI (A). The number of TSPO-positive cells at the injured site peaked at 4 days after SCI and significantly few-er TSPO-positive cells merged with GFP over time (B). Scale bars = 20 μm.
Figure 3
Figure 3
(A) PET and CT fusion images were created to detect the laminectomy level. (B) (R)-[11C]PK11195 PET images in the rat spinal cord injury model. (C) (R)-[11C]PK11195 uptake at the lesion level peaked at 4 days after SCI and was significantly higher compared to uptake in the control and sham groups. * p < 0.05.
Figure 4
Figure 4
(A) (R)-[3H]PK11195 autoradiography in the rat spinal cord injury model. (B) Accumulation of (R)-[3H]PK11195 peaked at 4 days after SCI and then gradually decreased in the dorsal horn of the injured spinal cord. Scale bars = 100 μm.
Figure 5
Figure 5
Clinical application of (R)-[11C]PK11195 PET/3T-MRI for patients with neuropathic pain. Data are shown for a healthy subject (A) and in patients examined at 4 weeks (B), at 10 months (C), and 9 years (D) after surgery. (R)-[11C]PK11195 uptake was apparent at 4 weeks and 10 months, but there was no significant (R)-[11C]PK11195 uptake at 9 years, despite the patient having severe neuropathic pain.
Figure 6
Figure 6
Relationship between standardized uptake value ratio (SUVR) and time after injury/surgery (A) and Neuropathic Pain System Inventory (NPSI) (B). SUVR was negatively correlated with time after injury/surgery and positively correlated with NPSI total score. Square markers: patients; Round marker: healthy subject; Outlined marker: excluded data for Pearson correlation analysis.
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