Mu Linjing, Krämer Stefanie D, Warnock Geoffrey I, Haider Achi, Bengs Susan, Cartolano Giovanni, Bräm Dominic S, Keller Claudia, Schibli Roger, Ametamey Simon M, Kaufmann Philipp A, Gebhard Catherine
Department of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
Department of Chemistry and Applied Biosciences, Radiopharmaceutical Sciences, Institute of Pharmaceutical Sciences, ETH Zurich, 8093, Zurich, Switzerland.
EJNMMI Res. 2020 Sep 29;10(1):114. doi: 10.1186/s13550-020-00700-7.
Clinical positron emission tomography (PET) imaging of the presynaptic norepinephrine transporter (NET) function provides valuable diagnostic information on sympathetic outflow and neuronal status. As data on the NET-targeting PET tracers [C]meta-hydroxyephedrine ([C]mHED) and [F]LMI1195 ([F]flubrobenguane) in murine experimental models are scarce or lacking, we performed a detailed characterization of their myocardial uptake pattern and investigated [C]mHED uptake by kinetic modelling.
[C]mHED and [F]LMI1195 accumulation in the heart was studied by PET/CT in FVB/N mice. To test for specific uptake by NET, desipramine, a selective NET inhibitor, was administered by intraperitoneal injection. [C]mHED kinetic modelling with input function from an arteriovenous shunt was performed in three mice.
Both tracers accumulated in the mouse myocardium; however, only [C]mHED uptake was significantly reduced by excess amount of desipramine. Myocardial [C]mHED uptake was half-saturated at 88.3 nmol/kg of combined mHED and metaraminol residual. After [C]mHED injection, a radiometabolite was detected in plasma and urine, but not in the myocardium. [C]mHED kinetics followed serial two-tissue compartment models with desipramine-sensitive K.
PET with [C]mHED but not [F]LMI1195 provides information on NET function in the mouse heart. [C]mHED PET is dose-independent in the mouse myocardium at < 10 nmol/kg of combined mHED and metaraminol. [C]mHED kinetics followed serial two-tissue compartment models with K representing NET transport. Myocardial [C]mHED uptake obtained from PET images may be used to assess cardiac sympathetic integrity in mouse models of cardiovascular disease.
对突触前去甲肾上腺素转运体（NET）功能进行临床正电子发射断层扫描（PET）成像可为交感神经流出和神经元状态提供有价值的诊断信息。由于关于NET靶向PET示踪剂[C]间羟基麻黄碱（[C]mHED）和[F]LMI1195（[F]氟苄胍）在小鼠实验模型中的数据稀缺或缺乏，我们对它们的心肌摄取模式进行了详细表征，并通过动力学建模研究了[C]mHED的摄取情况。
通过PET/CT研究了[C]mHED和[F]LMI1195在FVB/N小鼠心脏中的蓄积情况。为了测试NET的特异性摄取，通过腹腔注射给予选择性NET抑制剂地昔帕明。在三只小鼠中进行了具有动静脉分流输入函数的[C]mHED动力学建模。
两种示踪剂均在小鼠心肌中蓄积；然而，只有[C]mHED的摄取被过量的地昔帕明显著降低。心肌[C]mHED摄取在88.3 nmol/kg的联合mHED和间羟胺残留量时达到半饱和。注射[C]mHED后，在血浆和尿液中检测到一种放射性代谢物，但在心肌中未检测到。[C]mHED动力学遵循具有地昔帕明敏感K的连续双组织隔室模型。
[C]mHED PET而非[F]LMI1195 PET可提供小鼠心脏中NET功能的信息。在联合mHED和间羟胺<10 nmol/kg时，[C]mHED PET在小鼠心肌中与剂量无关。[C]mHED动力学遵循连续双组织隔室模型，其中K代表NET转运。从PET图像获得的心肌[C]mHED摄取可用于评估心血管疾病小鼠模型中的心脏交感神经完整性。
