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Translocator protein as an imaging marker of macrophage and stromal activation in rheumatoid arthritis pannus

Narayan, Nehal; Owen, David R.; Mandhair, Harpreet; Smyth, Erica; Carlucci, Francesco; Saleem, Azeem; Gunn, Roger N.; Rabiner, Eugenii A.; Wells, Lisa; Dakin, Stephanie G.; Sabokbar, Afsie; Taylor, Peter C.


Nehal Narayan

David R. Owen

Harpreet Mandhair

Erica Smyth

Francesco Carlucci

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Dr Azeem Saleem
Reader and Honorary Consultant in Clinical Oncology

Roger N. Gunn

Eugenii A. Rabiner

Lisa Wells

Stephanie G. Dakin

Afsie Sabokbar

Peter C. Taylor


PET radioligands targeted to translocator protein (TSPO) offer a highly sensitive and specific means of imaging joint inflammation in rheumatoid arthritis (RA). Through high expression of TSPO on activated macrophages, TSPO PET has been widely reported in several studies of RA as a means of imaging synovial macrophages in vivo. However, this premise does not take into account the ubiquitous expression of TSPO. This study aimed to investigate TSPO expression in major cellular constituents of RA pannus-monocytes, macrophages, fibroblastlike synoviocytes (FLS cells), and CD4-positive (CD41) T lymphocytes (T cells)-to more accurately interpret TSPO PET signal from RA synovium. Methods: Three RA patients and 3 healthy volunteers underwent PET of both knees using the TSPO radioligand 11 C-PBR28. Through 3 H-PBR28 autoradiography and immunostaining of synovial tissue in 6 RA patients and 6 healthy volunteers, cellular expression of TSPO in synovial tissue was evaluated. TSPO messenger RNA expression and 3 H-PBR28 radioligand binding was assessed using in vitro monocytes, macrophages, FLS cells, and CD41 T cells. Results: 11 C-PBR28 PET signal was significantly higher in RA joints than in healthy joints (average SUV, 0.82 ± 0.12 vs. 0.03 ± 0.004; P , 0.01). Further, 3 H-PBR28-specific binding in synovial tissue was approximately 10-fold higher in RA patients than in healthy controls. Immunofluorescence revealed TSPO expression on macrophages, FLS cells, and CD41 T cells. The in vitro study demonstrated the highest TSPO messenger RNA expression and 3 H-PBR28-specific binding in activated FLS cells, nonactivated M0 macrophages, and activated M2 reparative macrophages, with the least TSPO expression being in activated and nonactivated CD41 T cells. Conclusion: To our knowledge, this study was the first evaluation of cellular TSPO expression in synovium, with the highest TSPO expression and PBR28 binding being found on activated synovial FLS cells and M2 macrophages. TSPO-targeted PET may therefore have a unique sensitivity in detecting FLS cells and macrophage-predominant inflammation in RA, with potential utility for assessing treatment response in trials using novel FLS-cell-targeted therapies.


Narayan, N., Owen, D. R., Mandhair, H., Smyth, E., Carlucci, F., Saleem, A., …Taylor, P. C. (2018). Translocator protein as an imaging marker of macrophage and stromal activation in rheumatoid arthritis pannus. Journal of nuclear medicine, 59(7), 1125-1132.

Journal Article Type Article
Acceptance Date Nov 30, 2017
Online Publication Date Jan 4, 2018
Publication Date Jul 1, 2018
Deposit Date Jan 28, 2021
Journal Journal of Nuclear Medicine
Print ISSN 0161-5505
Electronic ISSN 2159-662X
Publisher Society of Nuclear Medicine
Peer Reviewed Peer Reviewed
Volume 59
Issue 7
Pages 1125-1132
Keywords Fibroblast-like synoviocytes; Macrophages; Translocator protein; Positron emission tomography
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