Imaging disease activity of rheumatoid arthritis by macrophage targeting using second generation translocator protein positron emission tomography tracers

PLoS One. 2019 Sep 25;14(9):e0222844. doi: 10.1371/journal.pone.0222844. eCollection 2019.


Background: Positron emission tomography (PET) imaging of macrophages using the translocator protein (TSPO) tracer (R)-[11C]PK11195 has shown the promise to image rheumatoid arthritis (RA). To further improve TSPO PET for RA imaging, second generation TSPO tracers [11C]DPA-713 and [18F]DPA-714 have recently been evaluated pre-clinically showing better imaging characteristics.

Objective: A clinical proof of concept study to evaluate [11C]DPA-713 and [18F]DPA-714 to visualize arthritis in RA patients.

Methods: RA patients (n = 13) with at least two active hand joints were included. PET/CT scans of the hands were obtained after injection of [18F]DPA-714, [11C]DPA-713 and/or (R)-[11C]PK11195 (max. 2 tracers pp). Standardized uptake values (SUVs) and target-to-background (T/B) ratios were determined. Imaging data of the 3 different tracers were compared by pooled post-hoc testing, and by a head to head comparison.

Results: Clinically active arthritis was present in 110 hand joints (2-17 pp). Arthritic joints were visualized with both [11C]DPA-713 and [18F]DPA-714. Visual tracer uptake corresponded with clinical signs of arthritis in 80% of the joints. Mean absolute uptake in PET-positive joints was significantly higher for [11C]DPA-713 than for [18F]DPA-714, the latter being not significantly different from (R)-[11C]PK11195 uptake. Background uptake was lower for both DPA tracers compared with that of (R)-[11C]PK11195. Higher absolute uptake and lower background resulted in two-fold higher T/B ratios for [11C]DPA-713.

Conclusions: [11C]DPA-713 and [18F]DPA-714 visualize arthritic joints in active RA patients and most optimal arthritis imaging results were obtained for [11C]DPA-713. Second generation TSPO macrophage PET provides new opportunities for both early diagnosis and therapy monitoring of RA.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amides
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis*
  • Early Diagnosis
  • Female
  • Hand Joints / cytology
  • Hand Joints / diagnostic imaging
  • Humans
  • Isoquinolines
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Molecular Imaging / methods*
  • Positron Emission Tomography Computed Tomography / methods*
  • Proof of Concept Study
  • Pyrazoles / pharmacology
  • Pyrimidines / pharmacology
  • Radiopharmaceuticals / pharmacology
  • Receptors, GABA / metabolism*


  • (R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide
  • Amides
  • Isoquinolines
  • N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
  • Pyrazoles
  • Pyrimidines
  • Radiopharmaceuticals
  • Receptors, GABA
  • TSPO protein, human

Grants and funding

This investigator-initiated study was financially supported by the CTMM Translational Research IT (TraIT) project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.