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

Durga M S H Chandrupatla, Carla F M Molthoff, Adriaan A Lammertsma, Conny J van der Laken, Gerrit Jansen

Research output: Contribution to journalReview articleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)366-378
Number of pages13
JournalDrug delivery and translational research
Volume9
Issue number1
DOIs
Publication statusPublished - Feb 2019

Cite this

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title = "The folate receptor β as a macrophage-mediated imaging and therapeutic target in rheumatoid arthritis",
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.",
author = "Chandrupatla, {Durga M S H} and Molthoff, {Carla F M} and Lammertsma, {Adriaan A} and {van der Laken}, {Conny J} and Gerrit Jansen",
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The folate receptor β as a macrophage-mediated imaging and therapeutic target in rheumatoid arthritis. / Chandrupatla, Durga M S H; Molthoff, Carla F M; Lammertsma, Adriaan A; van der Laken, Conny J; Jansen, Gerrit.

In: Drug delivery and translational research, Vol. 9, No. 1, 02.2019, p. 366-378.

Research output: Contribution to journalReview articleAcademicpeer-review

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AU - Jansen, Gerrit

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AB - 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.

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