title: Brain uptake of a non-radioactive pseudo-carrier and its effect on the biodistribution of [(18)F]AV-133 in mouse brain.
abstract: BACKGROUND
  9-[(18)F]Fluoropropyl-(+)-dihydrotetrabenazine ([(18)F]AV-133) is a new PET imaging agent targeting vesicular monoamine transporter type II (VMAT2). To shorten the preparation of [(18)F]AV-133 and to make it more widely available, a simple and rapid purification method using solid-phase extraction (SPE) instead of high-pressure liquid chromatography (HPLC) was developed. The SPE method produced doses containing the non-radioactive pseudo-carrier 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149). The objectives of this study were to evaluate the brain uptake of AV-149 by UPLC-MS/MS and its effect on the biodistribution of [(18)F]AV-133 in the brains of mice.
  
  
  METHODS
  The mice were injected with a bolus including [(18)F]AV-133 and different doses of AV-149. Brain tissue and blood samples were harvested. The effect of different amounts of AV-149 on [(18)F]AV-133 was evaluated by quantifying the brain distribution of radiolabelled tracer [(18)F]AV-133. The concentrations of AV-149 in the brain and plasma were analyzed using a UPLC-MS/MS method.
  
  
  RESULTS
  The concentrations of AV-149 in the brain and plasma exhibited a good linear relationship with the doses. The receptor occupancy curve was fit, and the calculated ED50 value was 8.165mg/kg. The brain biodistribution and regional selectivity of [(18)F]AV-133 had no obvious differences at AV-149 doses lower than 0.1mg/kg. With increasing doses of AV-149, the brain biodistribution of [(18)F]AV-133 changed significantly.
  
  
  CONCLUSIONS
  The results are important to further support that the improved radiolabelling procedure of [(18)F]AV-133 using an SPE method may be suitable for routine clinical application.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Xianying
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Aifang
authors.initials: A
authors.lastname: Deng
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China; Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China. Electronic address: zhulin@bnu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China. Electronic address: qiao_jinping@bnu.edu.cn.
authors.forename: Jinping
authors.initials: J
authors.lastname: Qiao
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; C549477:florbenazine F 18; D013747:Tetrabenazine
keywords: Biodistribution; LC-MS/MS; Parkinson's disease; Pseudo-carrier; Vesicular monoamine transporter type II; [(18)F]AV-133