[11C]-PBR28 POSITRON EMISSION TOMOGRAPHY SIGNAL AS AN IMAGING BIOMARKER OF JOINT INFLAMMATION AND PAIN IN KNEE OSTEOATHRITIS
Bibliographic record
Abstract
[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. 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. 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). 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). 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".