Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 160, 2100 Copenhagen, Denmark.
Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Molecules. 2022 Jun 22;27(13):4022. doi: 10.3390/molecules27134022.
Radiolabeling of tetrazines has gained increasing attention due to their important role in pretargeted imaging or therapy. The most commonly used radionuclide in PET imaging is fluorine-18. For this reason, we have recently developed a method which enables the direct aromatic F-fluorination of tetrazines using stannane precursors through copper-mediated fluorinations. Herein, we further optimized this labeling procedure. 3-(3-fluorophenyl)-1,2,4,5-tetrazine was chosen for this purpose because of its high reactivity and respective limited stability during the labeling process. By optimizing parameters such as elution conditions, precursor amount, catalyst, time or temperature, the radiochemical yield (RCY) could be increased by approximately 30%. These conditions were then applied to optimize the RCY of a recently successfully developed and promising pretargeting imaging agent. This agent could be isolated in a decay corrected RCY of 14 ± 3% and Am of 201 ± 30 GBq/µmol in a synthesis time of 70 min. Consequently, the RCY increased by 27%.
由于四嗪在靶向成像或治疗中的重要作用，其放射性标记受到越来越多的关注。正电子发射断层扫描（PET）成像中最常用的放射性核素是氟-18。出于这个原因，我们最近开发了一种方法，该方法可以通过铜介导的氟化作用，使用锡烷前体直接进行四嗪的芳基 F-氟化。在此，我们进一步优化了该标记程序。选择 3-(3-氟苯基)-1,2,4,5-四嗪是因为其在标记过程中的高反应性和各自的有限稳定性。通过优化洗脱条件、前体用量、催化剂、时间或温度等参数，放射性化学产率（RCY）可提高约 30%。然后将这些条件应用于优化最近成功开发的有前途的靶向成像剂的 RCY。该试剂可以在 70 分钟的合成时间内，以衰变校正的 RCY 为 14±3%和 Am 为 201±30GBq/µmol 的方式分离出来。因此，RCY 提高了 27%。
