TY - JOUR
T1 - In-vivo monitoring of anti-folate therapy in arthritic rats using [18F]fluoro-PEG-folate and positron emission tomography
AU - Chandrupatla, Durga M.S.H.
AU - Jansen, Gerrit
AU - Vos, Ricardo
AU - Verlaan, Mariska
AU - Chen, Qingshou
AU - Low, Philip S.
AU - Windhorst, Albert D.
AU - Lammertsma, Adriaan A.
AU - van der Laken, Conny J.
AU - Molthoff, Carla F.M.
N1 - Funding Information:
This study was supported by the Center for Translational Molecular Medicine (CTMM; project—TRACER), VU University Medical Center—Cancer Center Amsterdam (CCA—PV13/87) and the Dutch Arthritis Association (Reumafonds NRF 09-01-404).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/5/31
Y1 - 2017/5/31
N2 - 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.
AB - 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.
KW - Folate receptor β
KW - Macrophages
KW - Methotrexate
KW - Rheumatoid arthritis
KW - [F]fluoro-PEG-folate
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UR - http://www.scopus.com/inward/citedby.url?scp=85019976291&partnerID=8YFLogxK
U2 - 10.1186/s13075-017-1325-x
DO - 10.1186/s13075-017-1325-x
M3 - Article
C2 - 28569209
AN - SCOPUS:85019976291
VL - 19
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
SN - 1478-6354
IS - 1
M1 - 114
ER -