Luurtsema G, Boersma H H, Schepers M, de Vries A M T, Maas B, Zijlma R, de Vries E F J, Elsinga P H
Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands.
EJNMMI Radiopharm Chem. 2017;1(1):7. doi: 10.1186/s41181-016-0009-1. Epub 2016 Apr 4.
6-[F]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 [F]F, produced from [O] via the double-shoot approach, leading to FDOPA with higher specific activity as compared to FDOPA which was synthesized, using [F]F produced from Ne, 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 [O] double-shoot radionuclide production method yielded significantly more [F]F with less carrier F than the conventional method starting from Ne. 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 [O] 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.
6-[F]氟-L-3,4-二羟基苯丙氨酸（FDOPA）是一种常用于检测神经内分泌肿瘤和脑肿瘤以及用于帕金森病鉴别诊断的放射性药物。为满足对FDOPA的需求，需要一种符合GMP的高产生产方法。因此，本研究旨在改进FDOPA的生产和质量控制程序，以便能够远距离分发该放射性药物。FDOPA是通过用[O]经双靶法产生的[F]F对三甲基锡前体进行亲电氟化制备的，与使用由Ne产生的[F]F合成的FDOPA相比，所得FDOPA具有更高的比活，而由Ne产生的[F]F合成的FDOPA比活较低。使用经过验证的超高效液相色谱（UPLC）系统对产品进行质量控制，并与传统高效液相色谱（HPLC）系统的质量控制进行比较。使用UPLC-MS鉴定杂质。
与从Ne开始的传统方法相比，[O]双靶放射性核素生产方法产生的[F]F显著更多，载体F更少。调整放射性标记参数后，可以获得大量具有更高比活的FDOPA。与HPLC相比，UPLC进行的质量控制速度更快，检测到的副产物更多。UPLC-MS显示，最重要的副产物是FDOPA-醌，而不是欧洲药典所建议的6-羟基多巴。
分别引入[O]双靶放射性核素生产方法和采用UPLC进行产品分析，显著改善了FDOPA的生产和质量控制。结果，FDOPA现在常规可用于临床实践和远距离分发。
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