临床应用的[18F]FDOPA的无hplc和基于盒的亲核生产。

IF 2 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
American journal of nuclear medicine and molecular imaging Pub Date : 2021-08-15 eCollection Date: 2021-01-01
Huailei Jiang, Manoj K Jain, Hancheng Cai
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引用次数: 0

摘要

放射性示踪剂3,4-二羟基-6-[18F]氟- l -苯丙氨酸(L-6-[18F]fluorodopa或[18F]FDOPA)广泛用于帕金森病、脑肿瘤、神经内分泌肿瘤、婴幼儿局灶性高胰岛素症等疾病的多巴胺代谢PET成像。2019年,[18F]FDOPA被美国FDA批准用于检测疑似帕金森综合征成年患者纹状体多巴胺能神经末梢。[18F]FDOPA在符合cGMP的条件下实现全自动化生产,需要一种方便可靠的方法来满足日益增长的临床需求。在这项研究中,我们报道了在完全符合cGMP的环境下,使用GE Fastlab 2模块和质量控制(QC)的盒式自动化生产[18F]FDOPA。简单地说,使用FDOPA Fastlab盒和固相萃取(SPE)纯化,通过亲核放射性氟化处理[18F]FDOPA的自动放射性合成。[18F]FDOPA在合成结束时(EOS)和验证运行后8 h进行QC检测,包括外观、pH、半衰期、放射化学纯度和特性、对映体纯度、化学杂质、分子活性、放射性浓度、过滤器完整性、内毒素和无菌性。连续三次生产[18F]FDOPA是可靠的,具有理想的放射化学产率和高放射化学/对映体纯度和摩尔活性。[18F]FDOPA未经校正的放射化学产率为9.3 ~ 9.8%,总合成时间为~140 min。[18F]FDOPA的放射化学纯度和对映体纯度均>99.9%,在EOS下的摩尔活性为2.1 ~ 3.9 Ci/μmol。在EOS和EOS后8 h的完整QC结果显示,生产的[18F]FDOPA在有效期8小时内符合临床使用的所有释放标准。连续三次的验证运行和QC结果证明了盒式生产[18F]FDOPA用于常规临床使用的有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

HPLC-free and cassette-based nucleophilic production of [<sup>18</sup>F]FDOPA for clinical use.

HPLC-free and cassette-based nucleophilic production of [<sup>18</sup>F]FDOPA for clinical use.

HPLC-free and cassette-based nucleophilic production of [18F]FDOPA for clinical use.

Radiotracer 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (L-6-[18F]fluorodopa or [18F]FDOPA) is widely used for PET imaging of dopamine metabolism in several diseases including Parkinson's Disease, brain tumor, neuroendocrine tumors, and focal hyperinsulinism of infancy. In 2019, [18F]FDOPA was approved by US FDA for detection of dopaminergic nerve terminals in the striatum of adult patients with suspected Parkinsonian Syndromes. A convenient and reliable method is desired for fully automated production of [18F]FDOPA under cGMP compliance to meet the increasing clinical need. In this study, we reported a cassette-based automated production of [18F]FDOPA using a GE Fastlab 2 module and the quality control (QC) under fully cGMP compliant environment. Briefly, automated radiosynthesis of [18F]FDOPA was processed via nucleophilic radio-fluorination using FDOPA Fastlab cassette and solid phase extraction (SPE) purification. The QC tests of [18F]FDOPA, including appearance, pH, half-life, radiochemical purity and identity, enantiomeric purity, chemical impurities, molecular activity, radioactive concentration, filter integrity, endotoxin, and sterility, were conducted at the end of synthesis (EOS) and 8 h after EOS during the validation runs. Three consecutive productions of [18F]FDOPA were reliably achieved with desired radiochemical yield and high radiochemical/enantiomeric purities and molar activity. The uncorrected radiochemical yields of [18F]FDOPA were 9.3-9.8% with a total synthesis time of ~140 min. Both radiochemical and enantiomeric purities of [18F]FDOPA were >99.9% and the molar activities were 2.1-3.9 Ci/μmole at EOS. The full QC results at EOS and 8 h after EOS showed that the produced [18F]FDOPA met all release criteria for clinical use within 8 hours of expiration time. Three consecutive validation runs and QC results demonstrated the efficacy of cassette-based production of [18F]FDOPA for routine clinical use.

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来源期刊
American journal of nuclear medicine and molecular imaging
American journal of nuclear medicine and molecular imaging RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-
自引率
4.00%
发文量
4
期刊介绍: The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.
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