A concisely automated synthesis of TSPO radiotracer [18F]FDPA based on spirocyclic iodonium ylide method and validation for human use
A concisely automated synthesis of TSPO radiotracer [18F]FDPA based on spirocyclic iodonium ylide method and validation for human use
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基于螺环碘叶立德 (SCIDY) 方法的 TSPO 放射性示踪剂 [18 F]FDPA 的简明自动化合成及人类使用验证
DOI：
10.1002/jlcr.3824
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发表时间：
2020-03-01
影响因子：
1.8
通讯作者：
Liang, Steven H.
中科院分区：
文献类型：
--
作者：
Wang, Lu;Yao, Shaobo;Liang, Steven H.
氟-18标记的N，N-二乙基-2-（2-（4-（2-氟乙氧基）苯基）-5，7-二甲基吡唑并[1，5-a]嘧啶-3-基）乙酰胺（[F-18]FDPA）是用于转运蛋白18 kDa（TSPO）的正电子发射断层扫描（PET）成像的有效和选择性放射性示踪剂。我们以前的体外和体内评价已经证明，这种示踪剂是有前途的进一步人类翻译。我们的研究解决了需要简化这种放射性示踪剂的自动合成，使其更容易获得广泛的临床评价和应用。在这里，我们成功地证明了一步放射性标记的[F-18]FDPA的基础上的一种新的螺环碘鎓叶立德（SCIDY）前体使用四正丁基铵甲磺酸盐（TBAOMs），这已经证明了最高的放射化学产率和摩尔活性从容易获得的[F-18]氟离子。在GE TRACERlab FX 2 N合成模块上完成亲核放射性同位素分析，并在非衰变校正下获得配制的[F-18]FDPA。（n.d.c）放射化学产率为15.6 +/-4.2%，摩尔活度为529.2 +/- 22.5 GBq/μ mol（14.3 +/- 0.6 Ci/μ mol），并经验证可用于人体。该方法有利于在市售合成模块中高效合成[F-18]FDPA，这将广泛适用于常规生产和广泛的临床PET成像研究。
Fluorine-18 labeled N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ([F-18]FDPA) is a potent and selective radiotracer for positron-emission tomography (PET) imaging of the translocator protein 18 kDa (TSPO). Our previous in vitro and in vivo evaluations have proven that this tracer is promising for further human translation. Our study addresses the need to streamline the automatic synthesis of this radiotracer to make it more accessible for widespread clinical evaluation and application. Here, we successfully demonstrate a one-step radiolabeling of [F-18]FDPA based on a novel spirocyclic iodonium ylide (SCIDY) precursor using tetra-n-butyl ammonium methanesulfonate (TBAOMs), which has demonstrated the highest radiochemical yields and molar activity from readily available [F-18]fluoride ion. The nucleophilic radiofluorination was completed on a GE TRACERlab FX2 N synthesis module, and the formulated [F-18]FDPA was obtained in nondecay corrected (n.d.c) radiochemical yields of 15.6 +/- 4.2%, with molar activities of 529.2 +/- 22.5 GBq/mu mol (14.3 +/- 0.6 Ci/mu mol) at the end of synthesis (60 minutes, n = 3) and validated for human use. This methodology facilitates efficient synthesis of [F-18]FDPA in a commercially available synthesis module, which would be broadly applicable for routine production and widespread clinical PET imaging studies.