Publication date: May 29, 2025

Multisystemic inflammation might be a key pathophysiologic mechanism in post-coronavirus disease 2019 (post-COVID) syndrome. N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a] pyrimidin-3-yl)acetamide ([F]DPA-714), which binds with high affinity the translocator protein (TSPO) receptor, is used as a marker of inflammation. Therefore, quantifying [F]DPA-714 uptake throughout the body could assess extracerebral inflammation in post-COVID syndrome. However, the pharmacokinetics of whole-body [F]DPA-714 uptake have not yet been assessed. Thus, before quantifying whole-body [F]DPA-714 uptake in post-COVID syndrome, the aim of this study was to identify the optimal pharmacokinetic model in different extracerebral organs. Methods: Thirty-nine post-COVID participants with high-affinity binding for TSPO with or without persistent complaints were enrolled from the prospective VeCosCO study. Whole-body dynamic [F]DPA-714 PET/CT scans (0-60 min after injection) were performed. Ascending aorta-based image-derived input functions were corrected with manual arterial blood samples to establish metabolite-corrected plasma input functions. Time-activity curves were derived from volumes of interest in the adrenal gland, bone, kidney, liver, lung, myocardium, pancreas, skeletal muscle, spleen, and thyroid. [F]DPA-714 kinetics were studied by nonlinear regression fitting of 1- and 2-tissue-compartment models with an additional blood volume parameter to the time-activity curves. Results: An irreversible single-tissue-compartment model was preferred in bone and skeletal muscle, a reversible 2-tissue-compartment model was preferred in kidney and lung, and a reversible single-tissue-compartment model was preferred in the other organs. Our results showed various levels of [F]DPA-714 uptake in the 10 extracerebral organs. The highest mean volume of distribution was found in myocardium (33. 27 +/- 11. 91 mL⋅cm), and the lowest mean volume of distribution was found in lung (5. 12 +/- 2. 85 mL⋅cm). The mean influx rate was higher in bone than in skeletal muscle (respectively, 0. 101 vs. 0. 052 mL⋅cm⋅min; P < 0. 001). Conclusion: The TSPO receptor is widely distributed over the entire body, with very high [F]DPA-714 uptake in several organs. An irreversible model in bone and skeletal muscle and a reversible model in the other organs were preferred to describe [F]DPA-714 kinetics. Further studies using [F]DPA-714 to assess extracerebral inflammation should consider these kinetic differences among TSPO-rich organs.

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