Krapf Philipp, Wicher Thomas, Zlatopolskiy Boris D, Ermert Johannes, Neumaier Bernd
Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, Germany.
Institute of Radiochemistry and Experimental Molecular Imaging, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
Pharmaceuticals (Basel). 2025 Jan 17;18(1):119. doi: 10.3390/ph18010119.
The radiotracer [F]JK-PSMA-7, a prostate cancer imaging agent for positron emission tomography (PET), was previously synthesized by indirect radiofluorination using an F-labeled active ester as a prosthetic group, which had to be isolated and purified before it could be linked to the pharmacologically active Lys-urea-Glu motif. Although this procedure could be automated on two-reactor modules like the GE TRACERLab FX2N (FXN) to afford the tracer in modest radiochemical yields (RCY) of 18-25%, it is unsuitable for cassette-based systems with a single reactor. To simplify implementation on an automated synthesis module, the radiosynthesis of [F]JK-PSMA-7 was devised as a one-pot, two-step reaction. The new method is based on direct ("late-stage") radiofluorination of an appropriate onium triflate precursor and subsequent deprotection with -phosphoric acid. It was successfully established on the cassette-based Trasis AllInOne (AIO) module. Overall, the new protocol enabled the production of [F]JK-PSMA-7 in activity yields of 39 ± 4% (RCY = 58%) with an overall synthesis time of about 1 h. In a single production run with an initial activity of 36-43 GBq, 13-19 GBq of [F]JK-PSMA-7 with a radiochemical purity of >99% was obtained. We have established a highly reliable, GMP-compliant process for the automated radiosynthesis of [F]JK-PSMA-7 on the Trasis AllinOne (AIO) synthesizer, ensuring consistent and efficient production of this radioligand.
放射性示踪剂[F]JK-PSMA-7是一种用于正电子发射断层扫描（PET）的前列腺癌成像剂，此前是通过间接放射性氟化法合成的，使用F标记的活性酯作为辅基，在将其与具有药理活性的Lys-urea-Glu基序连接之前，必须进行分离和纯化。尽管该过程可以在GE TRACERLab FX2N（FXN）等双反应器模块上实现自动化，以18%-25%的适度放射化学产率（RCY）获得示踪剂，但它不适用于单反应器的基于盒式的系统。为了简化在自动化合成模块上的实施，[F]JK-PSMA-7的放射合成设计为一锅两步反应。新方法基于对合适的三氟甲磺酸鎓前体进行直接（“后期”）放射性氟化，随后用磷酸脱保护。它已在基于盒式的Trasis AllInOne（AIO）模块上成功建立。总体而言，新方案能够以39±4%的活度产率（RCY = 58%）生产[F]JK-PSMA-7，总合成时间约为1小时。在一次初始活度为36-43 GBq的单次生产运行中，获得了13-19 GBq的[F]JK-PSMA-7，放射化学纯度>99%。我们已经在Trasis AllinOne（AIO）合成器上建立了一个高度可靠、符合GMP的[F]JK-PSMA-7自动化放射合成工艺，确保了这种放射性配体的一致和高效生产。
