The folate receptor β as a macrophage-mediated imaging and therapeutic target in rheumatoid arthritis

Drug Deliv Transl Res. 2019 Feb;9(1):366-378. doi: 10.1007/s13346-018-0589-2.


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.

Keywords: Folate receptor; Folate-conjugated drugs; Imaging; Macrophages; Positron emission tomography (PET); Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism*
  • Folate Receptor 2 / metabolism*
  • Folic Acid / metabolism
  • Folic Acid Antagonists / pharmacology
  • Folic Acid Antagonists / therapeutic use
  • Humans
  • Macrophages / metabolism*
  • Positron-Emission Tomography


  • FOLR2 protein, human
  • Folate Receptor 2
  • Folic Acid Antagonists
  • Folic Acid