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Imaging disease activity of rheumatoid arthritis by macrophage targeting using second generation translocator protein positron emission tomography tracers.
- Source :
-
PloS one [PLoS One] 2019 Sep 25; Vol. 14 (9), pp. e0222844. Date of Electronic Publication: 2019 Sep 25 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- 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.<br />Objective: A clinical proof of concept study to evaluate [11C]DPA-713 and [18F]DPA-714 to visualize arthritis in RA patients.<br />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.<br />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.<br />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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Aged
Amides
Arthritis, Rheumatoid blood
Early Diagnosis
Female
Hand Joints cytology
Hand Joints diagnostic imaging
Humans
Isoquinolines
Male
Middle Aged
Proof of Concept Study
Pyrazoles pharmacology
Pyrimidines pharmacology
Radiopharmaceuticals pharmacology
Arthritis, Rheumatoid diagnosis
Macrophages metabolism
Molecular Imaging methods
Positron Emission Tomography Computed Tomography methods
Receptors, GABA metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 31553762
- Full Text :
- https://doi.org/10.1371/journal.pone.0222844