First in man study of [18F]fluoro-PEG-folate PET: a novel macrophage imaging technique to visualize rheumatoid arthritis

Nicki J.F. Verweij; Maqsood Yaqub; Stefan T.G. Bruijnen; S. Pieplenbosch; Marieke M. ter Wee; Gerrit Jansen; Qingshou Chen; Philip S. Low; Albert D. Windhorst; Adriaan A. Lammertsma; Otto S. Hoekstra; Alexandre E. Voskuyl; Conny J. van der Laken

doi:10.1038/s41598-020-57841-x

First in man study of [¹⁸F]fluoro-PEG-folate PET: a novel macrophage imaging technique to visualize rheumatoid arthritis

Nicki J.F. Verweij, Maqsood Yaqub, Stefan T.G. Bruijnen, S. Pieplenbosch, Marieke M. ter Wee, Gerrit Jansen, Qingshou Chen, Philip S. Low, Albert D. Windhorst, Adriaan A. Lammertsma, Otto S. Hoekstra, Alexandre E. Voskuyl, Conny J. van der Laken

Houston Methodist

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

Abstract

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.

Original language	English (US)
Article number	1047
Pages (from-to)	1047
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-57841-x
State	Published - Jan 23 2020

Keywords

Aged
Arthritis, Rheumatoid/diagnosis
Early Diagnosis
Female
Fluorine Radioisotopes/pharmacokinetics
Folate Receptor 2/metabolism
Folic Acid/analogs & derivatives
Humans
Macrophages/physiology
Male
Middle Aged
Molecular Imaging/methods
Polyethylene Glycols/pharmacokinetics
Positron-Emission Tomography/methods
Synovial Membrane/diagnostic imaging

ASJC Scopus subject areas

General

Access to Document

10.1038/s41598-020-57841-x

Cite this

Verweij, N. J. F., Yaqub, M., Bruijnen, S. T. G., Pieplenbosch, S., ter Wee, M. M., Jansen, G., Chen, Q., Low, P. S., Windhorst, A. D., Lammertsma, A. A., Hoekstra, O. S., Voskuyl, A. E., & van der Laken, C. J. (2020). First in man study of [¹⁸F]fluoro-PEG-folate PET: a novel macrophage imaging technique to visualize rheumatoid arthritis. Scientific Reports, 10(1), 1047. Article 1047. https://doi.org/10.1038/s41598-020-57841-x

Verweij, NJF, Yaqub, M, Bruijnen, STG, Pieplenbosch, S, ter Wee, MM, Jansen, G, Chen, Q, Low, PS, Windhorst, AD, Lammertsma, AA, Hoekstra, OS, Voskuyl, AE & van der Laken, CJ 2020, 'First in man study of [¹⁸F]fluoro-PEG-folate PET: a novel macrophage imaging technique to visualize rheumatoid arthritis', Scientific Reports, vol. 10, no. 1, 1047, pp. 1047. https://doi.org/10.1038/s41598-020-57841-x

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title = "First in man study of [18F]fluoro-PEG-folate PET: a novel macrophage imaging technique to visualize rheumatoid arthritis",

abstract = "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.",

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author = "Verweij, \{Nicki J.F.\} and Maqsood Yaqub and Bruijnen, \{Stefan T.G.\} and S. Pieplenbosch and \{ter Wee\}, \{Marieke M.\} and Gerrit Jansen and Qingshou Chen and Low, \{Philip S.\} and Windhorst, \{Albert D.\} and Lammertsma, \{Adriaan A.\} and Hoekstra, \{Otto S.\} and Voskuyl, \{Alexandre E.\} and \{van der Laken\}, \{Conny J.\}",

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doi = "10.1038/s41598-020-57841-x",

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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.

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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.

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KW - Middle Aged

KW - Molecular Imaging/methods

KW - Polyethylene Glycols/pharmacokinetics

KW - Positron-Emission Tomography/methods

KW - Synovial Membrane/diagnostic imaging

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