Palard-Novello Xavier, Visser Denise, Yaqub Maqsood, van de Giessen Elsmarieke, den Hollander Marijke E, Windhorst Albert D, Verfaillie Sander C J, Knoop Hans, van Berckel Bart N M, Golla Sandeep S V, Tolboom Nelleke, Boellaard Ronald
CLCC Eugène Marquis, INSERM, LTSI-UMR 1099, University of Rennes, Rennes, France;
Radiology and Nuclear Medicine, Amsterdam UMC, location VU Medical Center, Amsterdam, The Netherlands.
J Nucl Med. 2025 Jul 1;66(7):1142-1148. doi: 10.2967/jnumed.124.268979.
Multisystemic inflammation might be a key pathophysiologic mechanism in post-coronavirus disease 2019 (post-COVID) syndrome. 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. 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. 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; < 0.001). 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.
多系统炎症可能是2019冠状病毒病后（新冠后）综合征的关键病理生理机制。二乙基-2-(2-(4-(2-氟乙氧基)phenyl)5,7-二甲基吡唑并[1,5-a]嘧啶-3-基)乙酰胺（[F]DPA-714）与转位蛋白（TSPO）受体具有高亲和力结合，被用作炎症标志物。因此，定量全身[F]DPA-714摄取可评估新冠后综合征的脑外炎症。然而，全身[F]DPA-714摄取的药代动力学尚未得到评估。因此，在定量新冠后综合征患者的全身[F]DPA-714摄取之前，本研究的目的是确定不同脑外器官中的最佳药代动力学模型。从前瞻性VeCosCO研究中招募了39名对TSPO具有高亲和力结合且有或无持续不适主诉的新冠后参与者。进行了全身动态[F]DPA-714 PET/CT扫描（注射后0至60分钟）。基于升主动脉的图像衍生输入函数用手动采集的动脉血样本进行校正，以建立代谢物校正的血浆输入函数。从肾上腺、骨骼、肾脏、肝脏、肺、心肌、胰腺、骨骼肌、脾脏和甲状腺的感兴趣区域得出时间-活性曲线。通过将单组织隔室模型和双组织隔室模型以及一个额外的血容量参数进行非线性回归拟合到时间-活性曲线来研究[F]DPA-714的动力学。在骨骼和骨骼肌中，不可逆单组织隔室模型更适用；在肾脏和肺中，可逆双组织隔室模型更适用；在其他器官中，可逆单组织隔室模型更适用。我们的结果显示在10个脑外器官中[F]DPA-714摄取水平各异。分布容积的最高平均值见于心肌（33.27±11.91 mL·cm），最低平均值见于肺（5.12±2.85 mL·cm）。骨骼中的平均流入率高于骨骼肌（分别为0.101对0.052 mL·cm·min；P<0.001）。TSPO受体广泛分布于全身，在几个器官中[F]DPA-714摄取非常高。在骨骼和骨骼肌中采用不可逆模型，在其他器官中采用可逆模型更适合描述[F]DPA-714的动力学。使用[F]DPA-714评估脑外炎症的进一步研究应考虑富含TSPO的器官之间的这些动力学差异。
