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An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
The folate receptor β as a macrophage-mediated imaging and therapeutic target in rheumatoid arthritis
Durga M S H Chandrupatla1, Carla F M Molthoff2, Adriaan A Lammertsma2
1Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Abstract:
Macrophages play a key role in the pathophysiology of rheumatoid arthritis (RA). Notably, positive correlations have been reported between synovial macrophage infiltration and disease activity as well as therapy outcome in RA patients. Hence, macrophages can serve as an important target for both imaging disease activity and drug delivery in RA. Folate receptor β (FRβ) is a glycosylphosphatidyl (GPI)-anchored plasma membrane protein being expressed on myeloid cells and activated macrophages. FRβ harbors a nanomolar binding affinity for folic acid allowing this receptor to be exploited for RA disease imaging (e.g., folate-conjugated PET tracers) and therapeutic targeting (e.g., folate antagonists and folate-conjugated drugs). This review provides an overview of these emerging applications in RA by summarizing and discussing properties of FRβ, expression of FRβ in relation to macrophage polarization, FRβ-targeted in vivo imaging modalities, and FRβ-directed drug targeting.
Insights
Macrophages are crucial in rheumatoid arthritis (RA) and can be targeted for imaging and drug delivery. Folate receptor β (FRβ) on macrophages offers a promising avenue for RA diagnosis and treatment strategies.
Area of Science:
- Immunology
- Biochemistry
- Radiology
Background:
- Macrophages are central to rheumatoid arthritis (RA) pathophysiology.
- Synovial macrophage infiltration correlates with RA disease activity and treatment outcomes.
- Macrophages represent a viable target for RA imaging and drug delivery.
Purpose of the Study:
- To review the emerging applications of Folate receptor β (FRβ) in rheumatoid arthritis.
- To discuss FRβ properties, expression in relation to macrophage polarization, and its utility in imaging and drug targeting.
Main Methods:
- Review of scientific literature on FRβ and its role in RA.
- Discussion of FRβ expression patterns on myeloid cells and activated macrophages.
- Analysis of FRβ-targeted imaging modalities and drug delivery systems.
Main Results:
- FRβ is expressed on activated macrophages in RA.
- FRβ's high affinity for folic acid enables targeted imaging (PET tracers) and therapy (drug conjugates).
- Emerging applications leverage FRβ for in vivo imaging and drug delivery in RA.
Conclusions:
- FRβ is a promising target for RA management.
- Targeting FRβ can enhance disease imaging and therapeutic interventions in rheumatoid arthritis.
- Further research into FRβ-directed strategies holds potential for improved RA patient outcomes.
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