[11C]-PBR28 positron emission tomography signal as an imaging marker of joint inflammation in knee osteoarthritis

Author:

Sandström Angelica12ORCID,Torrado-Carvajal Angel123ORCID,Morrissey Erin J.12ORCID,Kim Minhae12ORCID,Alshelh Zeynab12ORCID,Zhu Yehui12ORCID,Li Matthew D.2,Chang Connie Y.2,Jarraya Mohamed2,Akeju Oluwaseun4,Schrepf Andrew5ORCID,Harris Richard E.675,Kwon Young-Min8,Bedair Hany8,Chen Antonia F.9,Mercaldo Nathaniel D.1ORCID,Kettner Norman10,Napadow Vitaly1211,Toschi Nicola112,Edwards Robert R.13,Loggia Marco L.124ORCID

Affiliation:

1. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

2. Department of Radiology, Massachusetts General Hospital, Boston, MA, United States

3. Medical Image Analysis and Biometry Laboratory, Universidad Rey Juan Carlos, Madrid, Spain

4. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

5. Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, MI, United States

6. Susan Samueli Integrative Health Institute, School of Medicine, University of California at Irvine, Irvine CA, United States

7. Department of Anesthesiology and Perioperative Care, School of Medicine, University of California at Irvine, Irvine CA, United States

8. Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

9. Department of Orthopaedic Surgery, Brigham and Women's Hospital, Boston, MA, United States

10. Department of Radiology, Logan University, Chesterfield, MO, United States

11. Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA, United States

12. Department of Biomedicine and Prevention, University of Rome, “Tor Vergata,” Rome, Italy

13. Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

Abstract

Abstract Although inflammation is known to play a role in knee osteoarthritis (KOA), inflammation-specific imaging is not routinely performed. In this article, we evaluate the role of joint inflammation, measured using [11C]-PBR28, a radioligand for the inflammatory marker 18-kDa translocator protein (TSPO), in KOA. Twenty-one KOA patients and 11 healthy controls (HC) underwent positron emission tomography/magnetic resonance imaging (PET/MRI) knee imaging with the TSPO ligand [11C]-PBR28. 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 (eg, pain and Kellgren–Lawrence [KL] grades). Overall, KOA patients demonstrated elevated [11C]-PBR28 binding across all knee ROIs, compared with HC (all P's < 0.005). Specifically, PET signal was significantly elevated in both knees in patients with bilateral KOA symptoms (both P's < 0.01), and in the symptomatic knee (P < 0.05), but not the asymptomatic knee (P = 0.95) of patients with unilateral KOA symptoms. Positron emission tomography signal was higher in the most vs least painful knee (P < 0.001), and the difference in pain ratings across knees was proportional to the difference in PET signal (r = 0.74, P < 0.001). Kellgren–Lawrence 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 KOA and a link between joint inflammation and osteoarthritis-related pain severity.

Funder

Foundation for the National Institutes of Health

U.S. Department of Defense

NIH Office of the Director

National Center for Complementary and Integrative Health

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine,Neurology (clinical),Neurology

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