Whole-Body [¹⁸F]DPA-714 Kinetic Assessment Using PET/CT Scanner with Long Axial Field of View.

Abstract

Multisystemic inflammation might be a key pathophysiologic mechanism in post-coronavirus disease 2019 (post-COVID) syndrome. <i>N,N-</i>diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a] pyrimidin-3-yl)acetamide ([¹⁸F]DPA-714), which binds with high affinity the translocator protein (TSPO) receptor, is used as a marker of inflammation. Therefore, quantifying [¹⁸F]DPA-714 uptake throughout the body could assess extracerebral inflammation in post-COVID syndrome. However, the pharmacokinetics of whole-body [¹⁸F]DPA-714 uptake have not yet been assessed. Thus, before quantifying whole-body [¹⁸F]DPA-714 uptake in post-COVID syndrome, the aim of this study was to identify the optimal pharmacokinetic model in different extracerebral organs. <b>Methods:</b> 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 [¹⁸F]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. [¹⁸F]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. <b>Results:</b> 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 [¹⁸F]DPA-714 uptake in the 10 extracerebral organs. The highest mean volume of distribution was found in myocardium (33.27 ± 11.91 mL⋅cm^-3), and the lowest mean volume of distribution was found in lung (5.12 ± 2.85 mL⋅cm^-3). The mean influx rate was higher in bone than in skeletal muscle (respectively, 0.101 vs. 0.052 mL⋅cm^-3⋅min^-1; <i>P</i> < 0.001). <b>Conclusion:</b> The TSPO receptor is widely distributed over the entire body, with very high [¹⁸F]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 [¹⁸F]DPA-714 kinetics. Further studies using [¹⁸F]DPA-714 to assess extracerebral inflammation should consider these kinetic differences among TSPO-rich organs.