TY - JOUR

T1 - Labeling of highly reactive tetrazines using [ 18F]SuFEx

AU - Battisti, Umberto Maria Maria

AU - Muller, Marius

AU - García-Vázquez, Rocio

AU - Herth, Matthias

N1 - The work was supported by the Danmarks Frie Forskningsfond (1032-00177B) and the Lundbeck Foundation (grant R303-2018-3567).

PY - 2023

Y1 - 2023

N2 - Pretargeted imaging is an emerging technique to study the in vivo biodistribution of nanomedicines. Currently, the tetrazine ligation is considered the most promising bioorthogonal reaction for pretargeting. Recently, Zheng et al. described an ultrafast late-stage radiolabeling of tetrazines based on sulfur 18 F-fluoride exchange click chemistry ([ 18 F]SuFEx). However, bispyridyl and H-tetrazines-the most promising structures for in vivo pretargeted applications-cannot be labeled using the proposed reaction conditions as they lead to decomposition of the tetrazine core. Here, we report improved conditions that allow 18 F-labeling of bispyridyl and H-tetrazines using SuFEx. This strategy resulted in fast and efficient radiolabeling of highly reactive tetrazines with radiochemical conversions of up to 85%. This opens up the possibility to use SuFEx to 18 F-label tetrazines which are suitable for in vivo pretargeted imaging.

AB - Pretargeted imaging is an emerging technique to study the in vivo biodistribution of nanomedicines. Currently, the tetrazine ligation is considered the most promising bioorthogonal reaction for pretargeting. Recently, Zheng et al. described an ultrafast late-stage radiolabeling of tetrazines based on sulfur 18 F-fluoride exchange click chemistry ([ 18 F]SuFEx). However, bispyridyl and H-tetrazines-the most promising structures for in vivo pretargeted applications-cannot be labeled using the proposed reaction conditions as they lead to decomposition of the tetrazine core. Here, we report improved conditions that allow 18 F-labeling of bispyridyl and H-tetrazines using SuFEx. This strategy resulted in fast and efficient radiolabeling of highly reactive tetrazines with radiochemical conversions of up to 85%. This opens up the possibility to use SuFEx to 18 F-label tetrazines which are suitable for in vivo pretargeted imaging.

KW - bioorthogonal chemistry

KW - Fluorine-18

KW - radiochemistry

KW - SuFEx

KW - tetrazine

U2 - 10.1055/a-2147-9303

DO - 10.1055/a-2147-9303

M3 - Journal article

AN - SCOPUS:85167924029

JO - SYNLETT: Accounts and Rapid Communications in Chemical Synthesis

JF - SYNLETT: Accounts and Rapid Communications in Chemical Synthesis

SN - 0936-5214

ER -