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

English version

Autoři: S. T. G. Bruijnen ^aff001; N. J. F. Verweij ^aff001; Y. Y. J. Gent ^aff001; M. C. Huisman ^aff002; A. D. Windhorst ^aff002; M. Kassiou ^aff003; P. M. van de Ven ^aff004; A. A. Lammertsma ^aff002; O. S. Hoekstra ^aff002; A. E. Voskuyl ^aff001; C. J. van der Laken ^aff001
Působiště autorů: Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam UMC| location VUmc, Amsterdam, the Netherlands ^aff001; Department of Radiology & Nuclear Medicine, Amsterdam UMC| location VUmc, Amsterdam, The Netherlands ^aff002; School of Chemistry, The University of Sydney, Sydney, Australia ^aff003; Department of Epidemiology and Biostatistics, Amsterdam UMC| location VUmc, Amsterdam, The Netherlands ^aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0222844

Souhrn

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.

Klíčová slova:

Arthritis – Rheumatoid arthritis – Blood – Macrophages – Skeletal joints – NSAIDs – Positron emission tomography

Zdroje

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