The positron emitting isotope fluorine-18 (18F) possesses almost ideal physicochemical properties for the development of radiotracers for diagnostic molecular imaging employing positron emission tomography (PET). 18F in its nucleophilic anionic 18F− form is usually prepared by bombarding an enriched 18O water target with protons of various energies between 5 and 20 MeV depending on the technical specifications of the cyclotron. Large thick-target yields between 5 and 14 GBq/µA can be obtained, enough to prepare large batches of radiotracers capable to serve a considerable contingent of patients (50 + per clinical batch). The overall yield of the radiotracer however depends on the efficiency of the 18F labeling chemistry. The Silicon Fluoride Acceptor chemistry (SiFA) has introduced a convenient and highly efficient way to provide clinical peptide-based 18F-radiotracers in a kit-like procedure matching the convenience of 99mTc radiopharmaceuticals. A radiotracer’s clinical success primarily hinges on whether its synthesis can be automated. Due to its simplicity, the SiFA chemistry, which is based on isotopic exchange (18F for 19F), does not only work in a manual setup but has been proven to be automatable, yielding large batches of 18F-radiotracers of high molar activity (Am). The production of SiFA radiotracer can be centralized and the radiopharmaceutical be distributed via the “satellite” principle, where one production facility economically serves multiple clinical application sites. Clinically validated tracers such as [18F]SiTATE and [18F]Ga-rhPSMA-7/-7.3 have been synthesized in an automated synthesis unit under good manufacturing practice conditions and used in large patient cohorts. Communication of common guidelines and practices is warranted to further the dissemination of SiFA radiopharmaceuticals and to give easy access to this technology. This current review highlights the most recent achievements in SiFA radiopharmaceutical automation geared towards large batch production for clinical application. Best practice advice and guidance towards a facilitated implementation of the SiFA technology into new and already operating PET tracer production facilities is provided. A brief outlook spotlights the future potential of SiFA radiochemistry within the landscape of non-canonical labeling chemistries.

中文翻译：

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18F-SiFA放射性药物自动化生产的良好实践

正电子发射同位素氟 18 (18F) 具有几乎理想的物理化学性质，可用于开发用于采用正电子发射断层扫描 (PET) 进行诊断分子成像的放射性示踪剂。亲核阴离子 18F− 形式的 18F 通常是通过用 5 至 20 MeV 之间各种能量的质子轰击富集 18O 水靶来制备的，具体取决于回旋加速器的技术规格。可以获得 5 至 14 GBq/μA 之间的大厚靶产量，足以制备大批量的放射性示踪剂，能够服务相当多的患者（每个临床批次 50+）。然而，放射性示踪剂的总产率取决于 18F 标记化学的效率。氟化硅受体化学 (SiFA) 引入了一种方便高效的方法，以类似试剂盒的程序提供基于临床肽的 18F 放射性示踪剂，与 99mTc 放射性药物的便利性相匹配。放射性示踪剂的临床成功主要取决于其合成是否可以自动化。由于其简单性，基于同位素交换（18F 换 19F）的 SiFA 化学不仅可以手动设置，而且已被证明是可自动化的，可产生大批量的高摩尔活性的 18F 放射性示踪剂（Am ）。SiFA放射性示踪剂的生产可以集中化，放射性药物可以通过“卫星”原理进行分配，其中一个生产设施可以经济地服务于多个临床应用场所。[18F]SiTATE 和 [18F]Ga-rhPSMA-7/-7.3 等经过临床验证的示踪剂已在良好生产实践条件下在自动合成装置中合成，并用于大型患者群体。有必要交流共同准则和实践，以进一步传播 SiFA 放射性药物并方便地获取该技术。本次综述重点介绍了 SiFA 放射性药物自动化在面向临床应用大批量生产方面取得的最新成就。提供最佳实践建议和指导，以促进 SiFA 技术在新的和已运行的 PET 示踪剂生产设施中的实施。简要展望强调了 SiFA 放射化学在非规范标记化学领域的未来潜力。