TY - JOUR

T1 - Optimization of Direct Aromatic 18F‐Labeling of Tetrazines

AU - Andersen, Ida Vang

AU - García‐vázquez, Rocío

AU - Battisti, Umberto Maria

AU - Herth, Matthias M.

N1 - Funding Information: Funding: This research was funded by from the European Union’s Horizon 2020 research and in‐ novation program under the Marie Skłodowska‐Curie, grant agreement No. 813528. MMH have received funding from the European Union’s EU Framework Programme for Research and Innova‐ tion Horizon 2020, grant agreement No. 670261. The Lundbeck Foundation, the Novo Nordisk Foundation, the Innovation Fund Denmark, and the Research Council for Independent Research are further acknowledged. Funding Information: This research was funded by from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska‐Curie, grant agreement No. 813528. MMH have received funding from the European Union’s EU Framework Programme for Research and Innovation Horizon 2020, grant agreement No. 670261. The Lundbeck Foundation, the Novo Nordisk Foundation, the Innovation Fund Denmark, and the Research Council for Independent Research are further acknowledged.

PY - 2022

Y1 - 2022

N2 - 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 aromatic18F‐ 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%.

AB - 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 aromatic18F‐ 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%.

KW - copper‐mediated fluorination

KW - fluorine‐18

KW - pretargeted imaging

KW - tetrazine ligation

U2 - 10.3390/molecules27134022

DO - 10.3390/molecules27134022

M3 - Journal article

C2 - 35807267

AN - SCOPUS:85133178744

VL - 27

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 13

M1 - 4022

ER -