TY - JOUR
T1 - First in man study of [18F]fluoro-PEG-folate PET
T2 - a novel macrophage imaging technique to visualize rheumatoid arthritis
AU - Verweij, Nicki J.F.
AU - Yaqub, Maqsood
AU - Bruijnen, Stefan T.G.
AU - Pieplenbosch, S.
AU - ter Wee, Marieke M.
AU - Jansen, Gerrit
AU - Chen, Qingshou
AU - Low, Philip S.
AU - Windhorst, Albert D.
AU - Lammertsma, Adriaan A.
AU - Hoekstra, Otto S.
AU - Voskuyl, Alexandre E.
AU - van der Laken, Conny J.
N1 - Funding Information:
We would like to thank Rolph van der Kooij for his contributions to the study as a radiochemist, Robert Schuit for his help analysing the blood data, Judith van Es for all of her time and effort in planning the different substudies and Merel van Dijk-Baak and Ewa Platek for excellent patient care during the comparative substudy. This study is investigator-initiated, and was financially supported by the CTMM TRACER project and ZonMw.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/1/23
Y1 - 2020/1/23
N2 - Non-invasive imaging of arthritis activity in rheumatoid arthritis (RA) patients using macrophage PET holds promise for early diagnosis and therapeutic response monitoring. Previously obtained results with macrophage tracer (R)-[11C]PK11195 were encouraging, but the imaging signal could be further improved by reduction of background uptake. Recently, the novel macrophage tracer [18F]fluoro-PEG-folate was developed. This tracer showed excellent targeting of the folate receptor β on activated macrophages in synovial tissue in a preclinical arthritic rat model. We performed three substudies to investigate the biodistribution, potential for imaging arthritis and kinetic properties of [18F]fluoro-PEG-folate in RA patients. Firstly, biodistribution demonstrated fast clearance of [18F]fluoro-PEG-folate from heart and blood vessels and no dose limiting uptake in organs. Secondly, [18F]fluoro-PEG-folate showed uptake in arthritic joints with significantly lower background and hence significantly higher target-to-background ratios as compared to reference macrophage tracer (R)-[11C]PK11195. Lastly, dynamic scanning demonstrated fast tracer uptake in affected joints, reaching a plateau after 1 minute, co-existing with a rapid blood clearance. In conclusion, this first in man study demonstrates the potential of [18F]fluoro-PEG-folate to image arthritis activity in RA with favourable imaging characteristics of rapid clearance and low background uptake, that allow for detection of inflammatory activity in the whole body.
AB - Non-invasive imaging of arthritis activity in rheumatoid arthritis (RA) patients using macrophage PET holds promise for early diagnosis and therapeutic response monitoring. Previously obtained results with macrophage tracer (R)-[11C]PK11195 were encouraging, but the imaging signal could be further improved by reduction of background uptake. Recently, the novel macrophage tracer [18F]fluoro-PEG-folate was developed. This tracer showed excellent targeting of the folate receptor β on activated macrophages in synovial tissue in a preclinical arthritic rat model. We performed three substudies to investigate the biodistribution, potential for imaging arthritis and kinetic properties of [18F]fluoro-PEG-folate in RA patients. Firstly, biodistribution demonstrated fast clearance of [18F]fluoro-PEG-folate from heart and blood vessels and no dose limiting uptake in organs. Secondly, [18F]fluoro-PEG-folate showed uptake in arthritic joints with significantly lower background and hence significantly higher target-to-background ratios as compared to reference macrophage tracer (R)-[11C]PK11195. Lastly, dynamic scanning demonstrated fast tracer uptake in affected joints, reaching a plateau after 1 minute, co-existing with a rapid blood clearance. In conclusion, this first in man study demonstrates the potential of [18F]fluoro-PEG-folate to image arthritis activity in RA with favourable imaging characteristics of rapid clearance and low background uptake, that allow for detection of inflammatory activity in the whole body.
KW - Aged
KW - Arthritis, Rheumatoid/diagnosis
KW - Early Diagnosis
KW - Female
KW - Fluorine Radioisotopes/pharmacokinetics
KW - Folate Receptor 2/metabolism
KW - Folic Acid/analogs & derivatives
KW - Humans
KW - Macrophages/physiology
KW - Male
KW - Middle Aged
KW - Molecular Imaging/methods
KW - Polyethylene Glycols/pharmacokinetics
KW - Positron-Emission Tomography/methods
KW - Synovial Membrane/diagnostic imaging
UR - http://www.scopus.com/inward/record.url?scp=85078154548&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078154548&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-57841-x
DO - 10.1038/s41598-020-57841-x
M3 - Article
C2 - 31974480
AN - SCOPUS:85078154548
VL - 10
SP - 1047
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 1047
ER -