Chen Zhengping, Tang Jie, Liu Chunyi, Li Xiaomin, Huang Hongbo, Xu Xijie, Yu Huixin
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China, 214063.
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China, 214063.
Nucl Med Biol. 2016 Jan;43(1):124-129. doi: 10.1016/j.nucmedbio.2015.09.009. Epub 2015 Oct 3.
The in vivo binding analysis of vesicular monoamine transporter type 2 (VMAT2) to radioligand has provided a means of investigating related disorders. Anesthesia is often inevitable when the investigations are performed in animals. In the present study, we tested effects of four commonly-used anesthetics: isoflurane, pentobarbital, chloral hydrate and ketamine, on in vivo VMAT2 binding to (18)F-FP-(+)-DTBZ, a specific VMAT2 radioligand, in rat brain.
The transient equilibrium time window for in vivo binding of (18)F-FP-(+)-DTBZ after a bolus injection was firstly determined. The brain biodistribution studies under anesthetized and awake rats were then performed at the equilibrium time. Standard uptake values (SUVs) of the interest brain regions: the striatum (ST), hippocampus (HP), cortex (CX) and cerebellum (CB) were obtained; and ratios of tissue to cerebellum were calculated.
Isoflurane and pentobarbital did not alter distribution of (18)F-FP-(+)-DTBZ in the brain relative to the awake group; neither SUVs nor ratios of ST/CB and HP/CB were altered significantly. Chloral hydrate significantly increased SUVs of all the brain regions, but did not significantly alter ratios of ST/CB and HP/CB. Ketamine significantly increased SUVs of the striatum, hippocampus and cortex, and insignificantly increased the SUV of the cerebellum; consequently, ketamine significantly increased ratios of ST/CB and HP/CB.
It is concluded that in vivo VMAT2 binding to (18)F-FP-(+)-DTBZ are not altered by isoflurane and pentobarbital, but altered by chloral hydrate and ketamine. Isoflurane and pentobarbital may be promising anesthetic compounds for investigating in vivo VMAT2 binding. Further studies are warranted to investigate the interactions of anesthetics with VMAT2 binding potential with in vivo PET studies.
囊泡单胺转运体2（VMAT2）与放射性配体的体内结合分析为研究相关疾病提供了一种手段。在动物身上进行研究时，麻醉往往不可避免。在本研究中，我们测试了四种常用麻醉剂：异氟烷、戊巴比妥、水合氯醛和氯胺酮，对大鼠脑中VMAT2与特异性VMAT2放射性配体（18）F-FP-（+）-DTBZ的体内结合的影响。
首先确定推注注射后（18）F-FP-（+）-DTBZ体内结合的瞬态平衡时间窗。然后在平衡时间对麻醉和清醒大鼠进行脑生物分布研究。获取感兴趣脑区：纹状体（ST）、海马体（HP）、皮质（CX）和小脑（CB）的标准摄取值（SUV）；并计算组织与小脑的比值。
相对于清醒组，异氟烷和戊巴比妥未改变（18）F-FP-（+）-DTBZ在脑中的分布；ST/CB和HP/CB的SUV及比值均未显著改变。水合氯醛显著增加了所有脑区的SUV，但未显著改变ST/CB和HP/CB的比值。氯胺酮显著增加了纹状体、海马体和皮质的SUV，对小脑的SUV增加不显著；因此，氯胺酮显著增加了ST/CB和HP/CB的比值。
得出结论，体内VMAT2与（18）F-FP-（+）-DTBZ的结合不受异氟烷和戊巴比妥的影响，但受水合氯醛和氯胺酮的影响。异氟烷和戊巴比妥可能是用于研究体内VMAT2结合的有前景的麻醉化合物。有必要进行进一步研究，通过体内正电子发射断层扫描研究来探究麻醉剂与VMAT2结合潜力的相互作用。
