Optimization of Direct Aromatic 18F-Labeling of Tetrazines

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-18-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/mu mol in a synthesis time of 70 min. Consequently, the RCY increased by 27%.

Automated summary

The radiolabeling of tetrazines was optimized in this study, leading to an increased radiochemical yield. The optimized conditions were applied to a pretargeting imaging agent and achieved promising results.