背景:(S)-[18F]FETrp是一种有前途的PET放射性示踪剂,用于对IDO1活动进行成像,色氨酸代谢的主要酶之一,在包括癌症在内的多种疾病中起关键作用。迄今为止,由于在亲核放射性氟化步骤期间发生的部分外消旋化,这种色氨酸类似物的放射性合成仍然具有很大的挑战性。这项工作旨在开发一种短,(S)-[18F]FETrp从相应的对映体纯甲苯磺酸盐前体的无差向异构化和有效的自动化程序。
结果:从相应的Na-Boc-(L和D)-色氨酸中获得了对映体纯的(S)-和(R)-FETrp参考以及甲苯磺酸前体(S)-和(R)-32和4个步骤,分别。放射性标记条件的手动优化导致>90%的放射化学转化和超过99%的对映体纯度。基于这些结果,(S)-[18F]FETrp放射合成在SynChromR&DEVOI模块上完全自动化,以55.2±7.5%的放射化学产率产生放射示踪剂,99.9%放射化学纯度,99.1±0.5%对映体过量,摩尔活度为53.2±9.3GBq/µmol(n=3)。
结论:为了避免外消旋化和复杂的纯化过程,目前遇到的(S)-[18F]FETrp的放射合成,我们在此报告了重大改进,包括对映体纯的甲苯磺酸酯前体和参考化合物的通用合成以及用于(S)-[18F]FETrp的放射合成的方便的一锅两步自动化程序。这种优化和强大的生产方法可以促进对这种相关的PET放射性示踪剂进行成像IDO1活性的进一步研究。
BACKGROUND: (S)-[18F]FETrp is a promising PET radiotracer for imaging IDO1 activity, one of the main enzymes involved in the tryptophan metabolism that plays a key role in several diseases including cancers. To date, the radiosynthesis of this tryptophan analogue remains highly challenging due to partial racemization occurring during the nucleophilic
radiofluorination step. This work aims to develop a short, epimerization-free and efficient automated procedure of (S)-[18F]FETrp from a corresponding enantiopure tosylate precursor.
RESULTS: Enantiomerically pure (S)- and (R)-FETrp references as well as tosylate precursors (S)- and (R)-3 were obtained from corresponding Na-Boc-(L and D)-tryptophan in 2 and 4 steps, respectively. Manual optimisation of the radiolabelling conditions resulted in > 90% radiochemical conversion with more than 99% enantiomeric purity. Based on these results, the (S)-[18F]FETrp radiosynthesis was fully automated on a SynChrom R&D EVOI module to produce the radiotracer in 55.2 ± 7.5% radiochemical yield, 99.9% radiochemical purity, 99.1 ± 0.5% enantiomeric excess, and molar activity of 53.2 ± 9.3 GBq/µmol (n = 3).
CONCLUSIONS: To avoid racemisation and complicated purification processes, currently encountered for the radiosynthesis of (S)-[18F]FETrp, we report herein significant improvements, including a versatile synthesis of enantiomerically pure tosylate precursor and reference compound and a convenient one-pot two-step automated procedure for the radiosynthesis of (S)-[18F]FETrp. This optimised and robust production method could facilitate further investigations of this relevant PET radiotracer for imaging IDO1 activity.