6-[18F]Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) is a frequently used radiopharmaceutical for detecting neuroendocrine and brain tumors and for the differential diagnosis of Parkinson’s disease. To meet the demand for FDOPA, a high-yield GMP-compliant production method is required. Therefore, this study aimed to improve the FDOPA production and quality control procedures to enable distribution of the radiopharmaceutical over distances. FDOPA was prepared by electrophilic fluorination of the trimethylstannyl precursor with [18F]F2, produced from [18O]2 via the double-shoot approach, leading to FDOPA with higher specific activity as compared to FDOPA which was synthesized, using [18F]F2 produced from 20Ne, leading to FDOPA with a lower specific activity. The quality control of the product was performed using a validated UPLC system and compared with quality control with a conventional HPLC system. Impurities were identified using UPLC-MS. The [18O]2 double-shoot radionuclide production method yielded significantly more [18F]F2 with less carrier F2 than the conventional method starting from 20Ne. After adjustment of radiolabeling parameters substantially higher amounts of FDOPA with higher specific activity could be obtained. Quality control by UPLC was much faster and detected more side-products than HPLC. UPLC-MS showed that the most important side-product was FDOPA-quinone, rather than 6-hydroxydopa as suggested by the European Pharmacopoeia. The production and quality control of FDOPA were significantly improved by introducing the [18O]2 double-shoot radionuclide production method, and product analysis by UPLC, respectively. As a result, FDOPA is now routinely available for clinical practice and for distribution over distances.

中文翻译：

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改进了 6-[18F]fluoro-L-DOPA 的符合 GMP 的多剂量生产和质量控制。

6-[18F] Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) 是一种常用的放射性药物，用于检测神经内分泌和脑肿瘤以及帕金森病的鉴别诊断。为了满足对 FDOPA 的需求，需要一种符合 GMP 的高产量生产方法。因此，本研究旨在改进 FDOPA 生产和质量控制程序，以实现放射性药物的远距离分布。FDOPA 是通过用 [18F]F2 对三甲基甲锡烷基前体进行亲电氟化来制备的，该前体由 [18O]2 通过双射方法产生，与使用 [18F]F2 产生的 FDOPA 合成的 FDOPA 相比，FDOPA 具有更高的比活性从 20Ne，导致 FDOPA 具有较低的比活性。使用经过验证的 UPLC 系统对产品进行质量控制，并与使用传统 HPLC 系统的质量控制进行比较。使用 UPLC-MS 鉴定杂质。与从 20Ne 开始的传统方法相比，[18O]2 双射放射性核素生产方法产生的 [18F]F2 显着更多，而载体 F2 更少。在调整放射性标记参数后，可以获得具有更高比活性的显着更高量的 FDOPA。与 HPLC 相比，UPLC 的质量控制速度更快，并且检测到的副产物更多。UPLC-MS 显示最重要的副产物是 FDOPA-醌，而不是欧洲药典建议的 6-羟基多巴。引入[18O]2双射核素生产方法，显着改善了FDOPA的生产和质量控制，和 UPLC 的产品分析，分别。因此，FDOPA 现在可以常规用于临床实践和远距离分布。