机构：[a]Key Laboratory of Radiopharmaceuticals (Beijing Normal University) Ministry of Education, Beijing, China[b]Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA[c]Department of Neurology, Beijing Xuanwu Hospital, Capital Medical University, Beijing, China神经内科首都医科大学宣武医院[d]Wincon Theracells Biotechnologies Co., Ltd. Nanning, China[e]Avid Radiopharmaceuticals, Inc., Philadelphia, PA, USA
Objectives: Recently, 9-[F-18]fluoropropyl-(+)-dihydrotetrabenazine (F-18-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 F-18-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 F-18-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 F-18-AV-133 uptake in the PD monkey brains and the effects of the pseudo-carrier on VMAT2 binding. Results: The radiochemical purity of the F-18-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 mu g/dose). The reduced uptake in the striatum of the lesioned monkey brains was confirmed by autoradiography. Ex vivo inhibition studies of F-18-AV-133 binding in rat brains, conducted with increasing amounts of AV-149, suggested that at the highest concentration (3.5 mg/kg) the VMAT2 binding in the striatum was only moderately blocked (20% reduction). Conclusions: The pseudo-carrier, AV-149, did not affect the F-18-AV-133/PET imaging of VMAT2 binding sites in normal or uni-laterally lesioned monkey brains. The new streamlined SPE purification method will enable F-18-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. (c) 2012 Elsevier Inc. All rights reserved.
基金：
973(2011CB504105)
863Programs Ministry of Science and Technology(SS2012AA020831)
National Institutes of Health (ROI-DK-081342)
第一作者机构：[a]Key Laboratory of Radiopharmaceuticals (Beijing Normal University) Ministry of Education, Beijing, China[b]Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
通讯作者：
通讯机构：[*1]Department of Radiology, University of Pennsylvania School of Medicine, 3700 Market Street, Suite 305, Philadelphia, PA 19104.
推荐引用方式(GB/T 7714)：
Lin Zhu,Hongwen Qiao,Brian P. Lieberman,et al.Imaging of VMAT2 binding sites in the brain by F-18-AV-133: The effect of a pseudo-carrier[J].NUCLEAR MEDICINE AND BIOLOGY.2012,39(7):897-904.doi:10.1016/j.nucmedbio.2012.05.002.
APA：
Lin Zhu,Hongwen Qiao,Brian P. Lieberman,Jingxiao Wu,Yajing Liu...&Hank F. Kung.(2012).Imaging of VMAT2 binding sites in the brain by F-18-AV-133: The effect of a pseudo-carrier.NUCLEAR MEDICINE AND BIOLOGY,39,(7)
MLA：
Lin Zhu,et al."Imaging of VMAT2 binding sites in the brain by F-18-AV-133: The effect of a pseudo-carrier".NUCLEAR MEDICINE AND BIOLOGY 39..7(2012):897-904
