title: Effects of anesthetics on vesicular monoamine transporter type 2 binding to ¹⁸F-FP-(+)-DTBZ: a biodistribution study in rat brain.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China, 214063. Electronic address: chenzhengping@jsinm.org.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China, 214063.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China, 214063.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China, 214063.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China, 214063.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Huang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China, 214063.
authors.forename: Xijie
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China, 214063.
authors.forename: Huixin
authors.initials: H
authors.lastname: Yu
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D000777:Anesthetics; D005462:Fluorine Radioisotopes; D050493:Vesicular Monoamine Transport Proteins; C549477:florbenazine F 18; D013747:Tetrabenazine
keywords: Anesthesia; Biodistribution; In vivo binding; Rat brain; VMAT2