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使用Raytest SynChrom研发模块自动生产[F]F-DOPA

Automatic Production of [F]F-DOPA Using the Raytest SynChrom R&D Module.

作者信息

Waśniowski Paweł, Czuczejko Jolanta, Chuchra Michał, Wędrowski Mateusz, Marciniak Dawid, Sobiak Stanisław, Małkowski Bogdan

机构信息

Department of Inorganic and Analytical Chemistry, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, ul. Jagiellonska 13-15, 85-067 Bydgoszcz, Poland.

Nuclear Medicine Department, Oncology Centre Professor Franciszek Łukaszczyk Memorial, dr I. Romanowskiej 2 Street, 85-796 Bydgoszcz, Poland.

出版信息

Pharmaceuticals (Basel). 2022 Dec 22;16(1):10. doi: 10.3390/ph16010010.

Abstract

[F]F-DOPA is widely used in PET diagnostics. Diseases diagnosed with this tracer are schizophrenia, Parkinson's disease, gliomas, neuroendocrine tumors, pheochromocytomas, and pancreatic adenocarcinoma. It should be noted that the [F]F-DOPA tracer has been known for over 30 years. However, the methods of radiosynthesis applied in the past did not allow its clinical use due to low efficiency and purity. Currently, in the market, one encounters different types of radiosynthesis using the fluorine F isotope and variants of the same method. The synthesis and its modifications were carried out using a Raytest Synchrom R&D module. The synthesis consists of the following steps: (a) binding of the fluoride anion F on an anion exchange column; (b) elution with TBAHCO; (c) nucleophilic fluorination to the ABX 1336 precursor; (d) purification of the intermediate product on the C18ec column; (e) Baeyer-Villiger oxidation; (f) hydrolysis; and (gfinal purification of the crude product on a semipreparative column. The nucleophilic synthesis of [F]F-DOPA was successfully performed in 120 min, using the ABX 1336 precursor on the Raytest SynChrom R&D module, with a radiochemical yield (RCY) of 15%, radiochemical purity (RCP) ≥ 97%, and enantiomeric purity (ee) ≥ 96%.

摘要

[F]F - 多巴广泛用于正电子发射断层扫描(PET)诊断。使用这种示踪剂诊断的疾病有精神分裂症、帕金森病、神经胶质瘤、神经内分泌肿瘤、嗜铬细胞瘤和胰腺腺癌。应当指出,[F]F - 多巴示踪剂已为人所知超过30年。然而,过去应用的放射性合成方法由于效率低和纯度低而无法用于临床。目前,在市场上,可以遇到使用氟F同位素的不同类型的放射性合成方法以及同一方法的变体。合成及其改进是使用Raytest Synchrom研发模块进行的。合成包括以下步骤:(a)氟阴离子F在阴离子交换柱上的结合;(b)用TBAHCO洗脱;(c)亲核氟化生成ABX 1336前体;(d)在C18ec柱上纯化中间产物;(e)拜耳 - 维利格氧化;(f)水解;以及(g)在半制备柱上对粗产物进行最终纯化。使用Raytest SynChrom研发模块,以ABX 1336前体在120分钟内成功完成了[F]F - 多巴的亲核合成,放射化学产率(RCY)为15%,放射化学纯度(RCP)≥97%,对映体纯度(ee)≥96%。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f3c/9865388/08c5922105df/pharmaceuticals-16-00010-g001.jpg

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