Imaging of VMAT2 binding sites in the brain by ¹⁸F-AV-133: The effect of a pseudo-carrier

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• 作者：Lin Zhu ; Hongwen Qiao ; Brian P. Lieberman ; Jingxiao Wu ; Yajing Liu ; Zhongyun Pan ; Karl Ploessl ; Seok Rye Choi ; Piu Chan ; Hank F. Kung
• 关键词：PET imaging ; Parkinson's disease ; Vesicular monoamine transporter 2 ; Brain imaging and pseudo-carrier effect
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：39
• 期：7
• 页码：897-904
• 全文大小：1172 K

文摘

Objectives

Recently, 9-[¹⁸F]fluoropropyl-(+)-dihydrotetrabenazine (¹⁸F-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 ¹⁸F-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 ¹⁸F-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 ¹⁸F-AV-133 uptake in the PD monkey brains and the effects of the pseudo-carrier on VMAT2 binding.

Results

The radiochemical purity of the ¹⁸F-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 ¦Ìg/dose). The reduced uptake in the striatum of the lesioned monkey brains was confirmed by autoradiography. Ex vivo inhibition studies of ¹⁸F-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 ¹⁸F-AV-133/PET imaging of VMAT2 binding sites in normal or uni-laterally lesioned monkey brains. The new streamlined SPE purification method will enable ¹⁸F-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.