title: Imaging of VMAT2 binding sites in the brain by (18)F-AV-133: the effect of a pseudo-carrier.
abstract: OBJECTIVE
  Recently, 9-[(18)F]fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV-133) was reported as a new vesicular monoamine transporter (VMAT2) imaging agent for diagnosis of Parkinson's disease (PD). To shorten the preparation of (18)F-AV-133 and to make it more widely available, we evaluated a simple, rapid purification with a solid-phase extraction method (SPE) using an Oasis HLB cartridge instead of high pressure liquid chromatography (HPLC). The SPE method produced doses containing a pseudo-carrier, 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149).
  
  
  METHODS
  To test the possible side effects of this pseudo-carrier, comparative dynamic PET scans of the brains of normal monkeys (2 each) and uni-laterally 6-OH-dopamine-lesioned PD monkeys (2 each) were performed using (18)F-AV-133 doses prepared by either SPE (containing pseudo-carrier) or HPLC (containing no pseudo-carrier). Autoradiographs of post mortem monkey brain sections were evaluated to confirm the relative (18)F-AV-133 uptake in the PD monkey brains and the effects of the pseudo-carrier on VMAT2 binding.
  
  
  RESULTS
  The radiochemical purity of the (18)F-AV-133, whether prepared by SPE or by HPLC, was excellent (>99%). PET scans of normal and PD monkey brains showed an expected reduction of VMAT2 in the lesioned areas of the striatum. It was not affected by the presence of the pseudo-carrier, AV-149 (maximally 250 μg/dose). The reduced uptake in the striatum of the lesioned monkey brains was confirmed by autoradiography. Ex vivo inhibition studies of (18)F-AV-133 binding in rat brains, conducted with increasing amounts of AV-149, suggested that at the highest concentration (3.5mg/kg) the VMAT2 binding in the striatum was only moderately blocked (20% reduction).
  
  
  CONCLUSIONS
  The pseudo-carrier, AV-149, did not affect the (18)F-AV-133/PET imaging of VMAT2 binding sites in normal or uni-laterally lesioned monkey brains. The new streamlined SPE purification method will enable (18)F-AV-133 to be widely available for routine clinical application in determining changes in monoamine neurons for patient with movement disorders or other psychiatric illnesses.
authors: Key Laboratory of Radiopharmaceuticals (Beijing Normal University) Ministry of Education, Beijing, China.
authors: Lin
authors: L
authors: Zhu
authors: Hongwen
authors: H
authors: Qiao
authors: Brian P
authors: BP
authors: Lieberman
authors: Jingxiao
authors: J
authors: Wu
authors: Yajing
authors: Y
authors: Liu
authors: Zhongyun
authors: Z
authors: Pan
authors: Karl
authors: K
authors: Ploessl
authors: Seok Rye
authors: SR
authors: Choi
authors: Piu
authors: P
authors: Chan
authors: Hank F
authors: HF
authors: Kung
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D004337:Drug Carriers / Q000494:pharmacology*; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D005462:Fluorine Radioisotopes; D050493:Vesicular Monoamine Transport Proteins; C549477:florbenazine F 18; D013747:Tetrabenazine