Assessment of the 18F-Labeled PET Tracer LMI1195 for Imaging Norepinephrine Handling in Rat Hearts
Assessment of the 18F-Labeled PET Tracer LMI1195 for Imaging Norepinephrine Handling in Rat Hearts
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DOI：
10.2967/jnumed.112.104232
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发表时间：
2013-07-01
影响因子：
9.3
通讯作者：
Nekolla, Stephan G.
中科院分区：
文献类型：
--
作者：
Higuchi, Takahiro;Yousefi, Behrooz H.;Nekolla, Stephan G.
一种新的F-18标记的示踪剂，LMI 1195（N-[3-溴-4-（3-F-18-氟-丙氧基）-苄基]-胍），正在开发用于交感神经成像;其对神经摄取-1机制的高度特异性先前已在细胞联合研究和评估心脏摄取的兔和非人灵长类动物研究中得到证实。本研究的目的是研究大鼠中F-18-LMI 1195心脏摄取的机制，已知其含有除摄取-1以外的去甲肾上腺素摄取机制。研究方法：通过定量体内PET成像研究了在健康雄性Wistar大鼠中静脉内施用F-18-LMI 1195后随时间推移在心脏中的示踪剂累积。通过用非选择性去甲肾上腺素摄取-1和去甲肾上腺素摄取-2抑制剂酚苄明（静脉内50 mg/kg; n = 4）、选择性去甲肾上腺素摄取-1抑制剂地昔帕明（静脉内2 mg/kg; n = 4）或盐水对照（静脉内; n = 4）预处理来评估摄取机制。结果如下：F-18-LMI 1195产生高和持续的心脏摄取，允许在示踪剂给药后60分钟内清晰描绘左心室壁。与对照组相比，用酚苄明预处理显著降低了F-18-LMI 1195的心脏摄取。相比之下，在地昔帕明预处理后保留了F-18-LMI 1195摄取。结论：在大鼠中，F-18-LMI 1195的心脏摄取被酚苄明而不是地昔帕明显著抑制，这表明F-18-LMI 1195是摄取-2机制的底物，并且与具有主导水平的机制的大鼠心脏一致。
A novel F-18-labeled tracer, LMI1195 (N-[3-bromo-4-(3-F-18-fluoro-propoxy)-benzyl]-guanidine), is being developed for sympathetic nerve imaging; its high specificity for neural uptake-1 mechanism has previously been demonstrated in cell associative studies and in rabbit and nonhuman primate studies assessing heart uptake. The aim of this study was to investigate the mechanisms of F-18-LMI1195 cardiac uptake in the rat, which is known to contain norepinephrine uptake mechanisms beyond uptake-1. Methods: Tracer accumulation in the heart was studied over time after intravenous administration of F-18-LMI1195 in healthy male Wistar rats by quantitative in vivo PET imaging. The uptake mechanism was assessed by pretreatment with the nonselective norepinephrine uptake-1 and norepinephrine uptake-2 inhibitor phenoxybenzamine (50 mg/kg intravenously; n = 4), the selective norepinephrine uptake-1 inhibitor desipramine (2 mg/kg intravenously; n = 4), or saline control (intravenously; n = 4). Results: F-18-LMI1195 produced high and sustained heart uptake allowing clear delineation of the left ventricular wall over 60 min after tracer administration. Pretreatment with phenoxybenzamine markedly reduced the F-18-LMI1195 cardiac uptake when compared with controls. In contrast, there was preserved F-18-LMI1195 uptake after desipramine pretreatment. Conclusion: In rats, cardiac uptake of F-18-LMI1195 was significantly inhibited by phenoxybenzamine but not desipramine, suggesting F-18-LMI1195 is a substrate for the uptake-2 mechanism and is consistent with the rat heart having a dominant level of the mechanism.