TY - JOUR
T1 - Folate Receptor Beta for Macrophage Imaging in Rheumatoid Arthritis
AU - Steinz, Maarten M.
AU - Ezdoglian, Aiarpi
AU - Khodadust, Fatemeh
AU - Molthoff, Carla F. M.
AU - Srinivasarao, Madduri
AU - Low, Philip S.
AU - Zwezerijnen, Gerben J. C.
AU - Yaqub, Maqsood
AU - Beaino, Wissam
AU - Windhorst, Albert D.
AU - Tas, Sander W.
AU - Jansen, Gerrit
AU - van der Laken, Conny J.
N1 - Funding Information: The work of this review was supported in part by grant from the Center for Translationational Molecular Medicine (CTMM TRACER), the Dutch Rheumatism Fund (ReumaNederland, Publisher Copyright: Copyright © 2022 Steinz, Ezdoglian, Khodadust, Molthoff, Srinivasarao, Low, Zwezerijnen, Yaqub, Beaino, Windhorst, Tas, Jansen and van der Laken.
PY - 2022/2/2
Y1 - 2022/2/2
N2 - Non-invasive imaging modalities constitute an increasingly important tool in diagnostic and therapy response monitoring of patients with autoimmune diseases, including rheumatoid arthritis (RA). In particular, macrophage imaging with positron emission tomography (PET) using novel radiotracers based on differential expression of plasma membrane proteins and functioning of cellular processes may be suited for this. Over the past decade, selective expression of folate receptor β (FRβ), a glycosylphosphatidylinositol-anchored plasma membrane protein, on myeloid cells has emerged as an attractive target for macrophage imaging by exploiting the high binding affinity of folate-based PET tracers. This work discusses molecular, biochemical and functional properties of FRβ, describes the preclinical development of a folate-PET tracer and the evaluation of this tracer in a translational model of arthritis for diagnostics and therapy-response monitoring, and finally the first clinical application of the folate-PET tracer in RA patients with active disease. Consequently, folate-based PET tracers hold great promise for macrophage imaging in a variety of (chronic) inflammatory (autoimmune) diseases beyond RA.
AB - Non-invasive imaging modalities constitute an increasingly important tool in diagnostic and therapy response monitoring of patients with autoimmune diseases, including rheumatoid arthritis (RA). In particular, macrophage imaging with positron emission tomography (PET) using novel radiotracers based on differential expression of plasma membrane proteins and functioning of cellular processes may be suited for this. Over the past decade, selective expression of folate receptor β (FRβ), a glycosylphosphatidylinositol-anchored plasma membrane protein, on myeloid cells has emerged as an attractive target for macrophage imaging by exploiting the high binding affinity of folate-based PET tracers. This work discusses molecular, biochemical and functional properties of FRβ, describes the preclinical development of a folate-PET tracer and the evaluation of this tracer in a translational model of arthritis for diagnostics and therapy-response monitoring, and finally the first clinical application of the folate-PET tracer in RA patients with active disease. Consequently, folate-based PET tracers hold great promise for macrophage imaging in a variety of (chronic) inflammatory (autoimmune) diseases beyond RA.
KW - PET imaging
KW - antigen-induced arthritis
KW - folate receptor beta
KW - macrophage
KW - rheumatoid arthritis
UR - http://www.scopus.com/inward/record.url?scp=85124911070&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2022.819163
DO - https://doi.org/10.3389/fimmu.2022.819163
M3 - Review article
C2 - 35185910
SN - 1664-3224
VL - 13
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 819163
ER -