Saba Wadad, Goutal Sébastien, Kuhnast Bertrand, Dollé Frédéric, Auvity Sylvain, Fontyn Yoan, Cayla Jérôme, Peyronneau Marie-Anne, Valette Héric, Tournier Nicolas
Inserm / CEA / Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, Orsay, F-91406, France.
Eur J Neurosci. 2015 Jul;42(1):1738-45. doi: 10.1111/ejn.12946. Epub 2015 Jun 22.
Translocator protein 18 kDa (TSPO) expression at the mitochondrial membrane of glial cells is related to glial activation. TSPO radioligands such as [(18)F]DPA-714 are useful for the non-invasive study of neuroimmune processes using positron emission tomography (PET). Anesthetic agents were shown to impact mitochondrial function and may influence [(18)F]DPA-714 binding parameters and PET kinetics. [(18) F]DPA-714 PET imaging was performed in Papio anubis baboons anesthetized using either intravenous propofol (n = 3) or inhaled isoflurane (n = 3). Brain kinetics and metabolite-corrected input function were measured to estimate [(18) F]DPA-714 brain distribution (VT). Displacement experiments were performed using PK11195 (1.5 mg/kg). In vitro [(18)F]DPA-714 binding experiments were performed using baboon brain tissue in the absence and presence of tested anesthetics. Brain radioactivity peaked higher in isoflurane-anesthetized animals compared with propofol (SUVmax = 2.7 ± 0.5 vs. 1.3 ± 0.2, respectively) but was not different after 30 min. Brain VT was not different under propofol and isoflurane. Displacement resulted in a 35.8 ± 8.4% decrease of brain radioactivity under propofol but not under isoflurane (0.1 ± 7.0%). In vitro, the presence of propofol increased TSPO density and dramatically reduced its affinity for [(18)F]DPA-714 compared with control. This in vitro effect was not significant with isoflurane. Exposure to propofol and isoflurane differentially influences TSPO interaction with its specific radioligand [(18)F]DPA-714 with subsequent impact on its tissue kinetics and specific binding estimated in vivo using PET. Therefore, the choice of anesthetics and their potential influence on PET data should be considered for the design of imaging studies using TSPO radioligands, especially in a translational research context.
18 kDa转位蛋白（TSPO）在神经胶质细胞线粒体膜上的表达与神经胶质细胞激活有关。TSPO放射性配体，如[（18）F]DPA - 714，可用于利用正电子发射断层扫描（PET）对神经免疫过程进行无创研究。已表明麻醉剂会影响线粒体功能，并可能影响[（18）F]DPA - 714的结合参数和PET动力学。对使用静脉注射丙泊酚（n = 3）或吸入异氟烷（n = 3）麻醉的东非狒狒进行了[（18）F]DPA - 714 PET成像。测量脑动力学和代谢物校正输入函数以估计[（18）F]DPA - 714在脑内的分布（VT）。使用PK11195（1.5 mg/kg）进行置换实验。在有无受试麻醉剂的情况下，使用狒狒脑组织进行体外[（18）F]DPA - 714结合实验。与丙泊酚麻醉的动物相比，异氟烷麻醉的动物脑放射性峰值更高（SUVmax分别为2.7±0.5和1.3±0.2），但30分钟后无差异。丙泊酚和异氟烷麻醉下脑VT无差异。置换导致丙泊酚麻醉下脑放射性降低35.8±8.4%，而异氟烷麻醉下无降低（0.1±7.0%）。在体外，与对照组相比，丙泊酚的存在增加了TSPO密度，并显著降低了其对[（18）F]DPA - 714的亲和力。异氟烷的这种体外效应不显著。丙泊酚和异氟烷暴露对TSPO与其特异性放射性配体[（18）F]DPA - 714的相互作用有不同影响，随后对其组织动力学和使用PET在体内估计的特异性结合产生影响。因此，在设计使用TSPO放射性配体的成像研究时，应考虑麻醉剂的选择及其对PET数据的潜在影响，尤其是在转化研究背景下。
