An improved preparation of [¹⁸F]FPBM: A potential serotonin transporter (SERT) imaging agent

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• 作者：Lin Zhu ; Genxun Li ; Seok Rye Choi ; Karl Pl枚ssl ; Piu Chan ; Hongwen Qiao ; Zhihao Zha ; Hank F. Kung
• 关键词：DASB ; (N ; N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ; (+)-McN5652 ; trans-1 ; 2 ; 3 ; 5 ; 6 ; 10-  ; < ;   ; beta  ; > ;   ; &minus ;   ; hexahydro-6-[4-(methylthio)phenyl-[pyrrolo-[2 ; 1-  ; < ;   ; alpha  ; > ; ]isoquinoline ; PET ; positron emission tomography ; SPECT ; single photon emission computed tomography ; nor-  ; < ;   ; beta  ; > ;   ; &minus ;   ; CIT ; 2  ; < ;   ; beta  ; > ;   ; &minus ;   ; carbomethoxy-3  ; < ;   ; beta  ; > ;   ; &minus ; (4-iodopheny
• 刊名：Nuclear Medicine and Biology
• 出版年：November, 2013
• 年：2013
• 卷：40
• 期：8
• 页码：974-979
• 全文大小：1140 K

文摘

4 class="h4">Introduction4>In vivo positron emission tomography (PET) imaging of the serotonin transporter (SERT) is a valuable tool in drug development and in monitoring brain diseases with altered serotonergic function. We have developed a two-step labeling reaction for the preparation of the high serotonin affinity ligand [¹⁸F]FPBM ([¹⁸F]2-(2鈥?((dimethylamino)methyl)-4鈥?(3-fluoropropoxy)phenylthio)benzenamine, 1).4 class="h4">Method4>

To improve and automate the radiolabeling of [¹⁸F]FPBM, 1, an intermediate, [¹⁸F]3-fluoropropyltosylate, [¹⁸F]4, was prepared first, and then it was reacted with the phenol precursor (4-(2-aminophenylthio)-3-((dimethylamino)methyl)phenol, 3) to afford [¹⁸F]FPBM, 1. To optimize the labeling, this O-alkylation reaction was evaluated under different temperatures, using different bases and varying amounts of precursor 3. The desired product was obtained after a solid phase extraction (SPE) purification.4 class="h4">Results4>

This two-step radiolabeling reaction successfully produced the desired [¹⁸F]FPBM, 1, with an excellent radiochemical purity (> 95%, n = 8). Radiochemical yields were between 31% and 39% (decay corrected, total time of labeling: 70 min, n = 8). The SPE purification cannot completely remove pseudo-carriers in the final dose of [¹⁸F]FPBM, 1. The concentrations of major pseudo-carriers were measured by UV-HPLC (476-676, 68-95 and 50-71 渭g for precursor 3, O-hydroxypropyl and O-allyloxy derivatives, 5 and 6, respectively). To investigate the potential inhibition of SERT binding of these pseudo-carriers, we performed in vitro competition experiments evaluated by autoradiography. Known amounts of 鈥榮tandard鈥?FPBM, 1, of the pseudo-carriers, 5 and 6, were added to the HPLC-purified [¹⁸F]1 dose. The inhibition of 鈥榮tandard鈥?FPBM, 1, binding to the SERT binding sites, using monkey brain sections, were measured (EC₅₀ = 13, 46, 7.1 and 8.3 nM, respectively for 1, precursor 3, O-hydroxypropyl and O-allyloxy derivative of 3).4 class="h4">Conclusion4>

An improved radiolabeling method by a SPE purification for preparation of [¹⁸F]FPBM, 1, was developed. The results suggest that it is feasible to use this labeling method to prepare [¹⁸F]FPBM, 1, without affecting in vivo SERT binding.