title: In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease.
abstract: BACKGROUND
  The utility of [(18)F]FPBM [2-(2'-((dimethylamino)methyl)-4'-(3-[(18)F]-fluoropropoxy)phenylthio)benzenamine], a selective serotonin transporter (SERT) tracer, and [(18)F]AV-133 [(+)-2-Hydroxy-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizine], a selective vesicular monoamine transporter 2 (VMAT2) tracer, were tested in the 6-hydroxydopamine (6-OHDA) unilateral lesioned rat model.
  
  
  METHODS
  Positron emission tomography (PET) imaging of three 6-OHDA unilateral lesioned male Sprague Dawley rats (Rats 1-3) were performed with [(18)F]FPBM and [(18)F]AV-133 to examine whether changes in SERT and VMAT2 binding, respectively, could be detected in the brain. The brains of the three rats were then removed and examined by in vitro autoradiography with [(18)F]FPBM and the dopamine transporter ligand, [(125)I]IPT [N-(3'-[(125)I]-iodopropen-2'-yl)-2-beta-carbomethoxy-3-beta-(4-chloro phenyl) tropane, for confirmation. Biodistribution of [(18)F]FPBM in a separate group of p-chloroamphetamine (PCA) treated rats were also performed.
  
  
  RESULTS
  PET image analysis showed varying levels of SERT binding reduction (Rat 1=-11%, Rat 2=-4%, Rat 3=-43%; n=2) and a clear and definitive loss of VMAT2 binding (Rat 1=-87%, Rat 2=-72%, and Rat 3=-91%; n=1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (p-chloroamphetamine) showed a significant reduction of [(18)F]FPBM uptake in the cortex and hypothalamus regions of the brain.
  
  
  CONCLUSIONS
  The preliminary data suggest that [(18)F]FPBM and [(18)F]AV-133 may be useful for the examination of serotonergic and dopaminergic neuron integrity, respectively, in the living brain.
authors.affiliation: Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Wang
authors.forename: Shunichi
authors.initials: S
authors.lastname: Oya
authors.forename: Ajit K
authors.initials: AK
authors.lastname: Parhi
authors.forename: Brian P
authors.initials: BP
authors.lastname: Lieberman
authors.forename: Karl
authors.initials: K
authors.lastname: Ploessl
authors.forename: Catherine
authors.initials: C
authors.lastname: Hou
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*; D010133:p-Chloroamphetamine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C527727:2-(2-((dimethylamino)methyl)-4-(3-fluoropropoxy)phenylthio)benzenamine; D000814:Aniline Compounds; D005462:Fluorine Radioisotopes; D011849:Radioactive Tracers; D050486:Serotonin Plasma Membrane Transport Proteins; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D010133:p-Chloroamphetamine; C549477:florbenazine F 18; D013747:Tetrabenazine
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