[11C]-PBR28 POSITRON EMISSION TOMOGRAPHY SIGNAL AS AN IMAGING BIOMARKER OF JOINT INFLAMMATION AND PAIN IN KNEE OSTEOATHRITIS

BACKGROUND

[¹¹C]-PBR28 is a positron emission tomography (PET) radioligand targeting the 18-kDa translocator protein (TSPO). The expression of this protein is highly upregulated in the central nervous system (CNS) during neuroinflammatory responses (mostly glial cells). TSPO PET radioligands are also expressed outside of the CNS in the peripheral/circulating immune cells. As a result, TSPO has been used as a marker of peripheral (in addition to central) inflammation. For instance, elevated uptake of [¹¹C]-PBR28 signal has been reported in ipsilateral lumbar neuroforamen, among patients with lumbar radiculopathy. Furthermore, a recent study among patients with rheumatoid arthritis showed significantly higher [¹¹C]-PBR28 signal in affected knees compared with healthy knee joints. The highest TSPO expression was reported on activated fibroblast-like synoviocytes as well as undifferentiated and reparative macrophages. However, no study has yet imaged [¹¹C]-PBR28 PET uptake in a group of knee osteoarthritis (OA) patients.

PURPOSE

To evaluate the role of TSPO as an imaging marker of peripheral noxious-driven knee pain among patients with advanced knee OA, and to test its associations with clinical variables.

METHODS

Twenty-one knee OA patients scheduled to undergo a total knee arthroplasty (TKA) and 11 healthy controls (HC) underwent positron emission tomography/magnetic resonance imaging (PET/MRI) knee imaging with the TSPO ligand [¹¹C]-PBR28. At the imaging visit, participants were asked to rate their average experienced pain intensity in the past week on a numerical rating scale (NRS), and to complete the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Preoperative knee radiographs were retrospectively scored for KL grade by a trained musculoskeletal radiologist. Standardized uptake values were extracted from regions-of-interest (ROIs) semiautomatically segmented from MRI data, and compared across groups (HC, KOA) and subgroups (unilateral/bilateral KOA symptoms), across knees (most vs least painful), and against clinical variables (e.g., pain and Kellgren–Lawrence [KL] grades). Statistical analyses were performed in R (Version 4.2.0).

RESULTS

Patients characteristics are shown in Table 1. Overall, knee OA patients demonstrated elevated [¹¹C]-PBR28 binding across all knee ROIs, compared with HC (all P's < 0.005). PET signal was higher in the most vs least painful knee (P < 0.001) (Figure 1), and the difference in pain ratings (NRS) across knees was proportional to the difference in PET signal (r = 0.74, P < 0.001). there were no significant associations between any of the WOMAC scores (subscores or total sum) and the PET signal of either left and right knees (averaged) (all R's = between -0.24 and -0.07; all P's>0.3) or the most painful knee (according to NRS) (all R's = - 0.25 to - 0.06; all P's > 0.3). KL grades neither correlated with PET signal (left knee r = 0.32, P = 0.19; right knee r = 0.18, P = 0.45) nor pain (r = 0.39, P = 0.07).

CONCLUSION

The current results support further exploration of [¹¹C]-PBR28 PET signal as an imaging marker candidate for knee OA and a link between joint inflammation and osteoarthritis-related pain severity.