In-vivo monitoring of anti-folate therapy in arthritic rats using [18F]fluoro-PEG-folate and positron emission tomography.

Abstract

BACKGROUND:

Folate receptor β (FRβ) is involved in facilitating cellular uptake of folates and anti-folates (such as methotrexate (MTX)). In rheumatoid arthritis, FRβ is expressed on synovial macrophages and recently has been explored as a biomarker for imaging in arthritic rats using the folate-based positron emission tomography (PET) tracer [18F]fluoro-PEG-folate. The purpose of this study was to examine whether this folate tracer can also be used to monitor therapeutic efficacy of MTX in arthritic rats.

METHODS:

Arthritic rats received either no treatment or MTX therapy (1 mg/kg, either 2× or 4×). Healthy rats did not receive any arthritic induction or therapy. [18F]fluoro-PEG-folate PET-CT scans (60 min) were performed before and after MTX therapy. Following PET, the ex-vivo tissue distribution of radioactivity was determined in excised knees and multiple tissues. Synovial macrophage infiltration in knee sections was quantified by immunohistochemistry using ED1 and ED2 antibodies.

RESULTS:

PET scans clearly visualized increased uptake of [18F]fluoro-PEG-folate in arthritic knees compared with contralateral knees. Significantly lower standard uptake values (1.5-fold, p < 0.01) were observed in arthritic knees of both MTX-treated groups after therapy, approximating the levels seen in healthy rats. Consistently, ex-vivo tissue distribution demonstrated a 2-4-fold lower tracer uptake in the arthritic knee of 2× and 4× MTX-treated rats, respectively, compared with control rats. These results were corroborated with significantly reduced (2-4-fold, p < 0.01) ED1-positive and ED2-positive synovial macrophages in arthritic knees of the MTX-treated rats compared with those of the control rats.

CONCLUSION:

This study in arthritic rats underscores the potential and usefulness of [18F]fluoro-PEG-folate PET as a therapeutic monitoring tool of MTX therapy and potentially other anti-folate treatment of arthritis.

• Authors: Durga M S H Chandrupatla, Gerrit Jansen, Ricardo Vos, Mariska Verlaan, Qingshou Chen, Philip S Low, Albert D Windhorst, Adriaan A Lammertsma, Conny J van der Laken, Carla F M Molthoff
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 19 Issue 1 Pg. 114 (05 31 2017) ISSN: 1478-6362 [Electronic] England
• PMID: 28569209 (Publication Type: Journal Article)

Chemical References

• Antirheumatic Agents
• Fluorine Radioisotopes
• poly(ethylene glycol)-folate
• Polyethylene Glycols
• Folic Acid
• Methotrexate

Topics

• Animals
• Antirheumatic Agents (pharmacology)
• Arthritis, Experimental (diagnostic imaging, drug therapy)
• Arthritis, Rheumatoid (drug therapy)
• Fluorine Radioisotopes
• Folic Acid (analogs & derivatives)
• Male
• Methotrexate (pharmacology)
• Polyethylene Glycols
• Positron-Emission Tomography (methods)
• Rats
• Rats, Wistar