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@article{Narayan:2018:10.2967/jnumed.117.202200,
author = {Narayan, N and Owen, D and Mandhair, H and Smyth, E and Carlucci, F and Saleem, A and Gunn, R and Rabiner, EIA and Wells, L and Dakin, S and Sabokbar, A and Taylor, P},
doi = {10.2967/jnumed.117.202200},
journal = {Journal of Nuclear Medicine},
pages = {1125--1132},
title = {Translocator protein as an imaging marker of macrophage and stromal activation in RA pannus},
url = {http://dx.doi.org/10.2967/jnumed.117.202200},
volume = {59},
year = {2018}
}

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TY  - JOUR
AB  - Positron Emission Tomography (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, fibroblast-like synoviocytes (FLS) and CD4+ T lymphocytes, to more accurately interpret TSPO PET signal from RA synovium. Methods: 3 RA patients and 3 healthy volunteers underwent PET both knees using the TSPO radioligand 11C-PBR28. Through synovial tissue 3H-PBR28 autoradiography and immunostaining of 6 RA patients and 6 healthy volunteers, cellular expression of TSPO in synovial tissue was evaluated. TSPO mRNA expression and 3H-PBR28 radioligand binding was assessed using in vitro monocytes, macrophages, FLS and CD4+ T-lymphocytes. Results:11C-PBR28 PET signal was significantly higher in RA compared to healthy joints (average SUV 0.82± 0.12 compared to 0.03± 0.004 respectively, p<0.01). Further, 3H-PBR28 specific binding in synovial tissue was approximately 10-fold higher in RA compared to healthy controls. Immunofluorescence revealed TSPO expression on macrophages, FLS and CD4+ T cells. In vitro study demonstrated highest TSPO mRNA expression and 3H-PBR28 specific binding, in activated FLS, non-activated and activated 'M2' reparative macrophages, with least TSPO expression in activated and non-activated CD4+ T lymphocytes. Conclusion: This study is the first evaluation of cellular TSPO expression in synovium, finding highest TSPO expression and PBR28 binding on activated synovial FLS and M2 phenotype macrophages. TSPO targeted PET may therefore have unique sensitivity to detect FLS and macropha
AU  - Narayan,N
AU  - Owen,D
AU  - Mandhair,H
AU  - Smyth,E
AU  - Carlucci,F
AU  - Saleem,A
AU  - Gunn,R
AU  - Rabiner,EIA
AU  - Wells,L
AU  - Dakin,S
AU  - Sabokbar,A
AU  - Taylor,P
DO  - 10.2967/jnumed.117.202200
EP  - 1132
PY  - 2018///
SN  - 1535-5667
SP  - 1125
TI  - Translocator protein as an imaging marker of macrophage and stromal activation in RA pannus
T2  - Journal of Nuclear Medicine
UR  - http://dx.doi.org/10.2967/jnumed.117.202200
UR  - http://hdl.handle.net/10044/1/57088
VL  - 59
ER  -

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