18F- IeDDA 18F- New 18F-labeled dienophiles and 18F-labeling method using IeDDA reaction with tetrazines

摘要

It relates to labeling technology of F-18 radioisotope using IeDDA (Inverse electron Demand Diels-Alder) reaction between tetrazine compound and dienophile, The ketone compound of the present invention easily forms an enamine in an aqueous solution together with a secondary amine and causes a very fast conjugation reaction with the tetrazine compound. In particular, the greater the amount of water in the aqueous solution, the better the reaction proceeds, so it has the advantage of being suitable for biological compounds such as peptides and antibodies. In addition, unlike the existing reaction that forms several stereoisomers, only a small amount of one structural isomer is generated in addition to the main product, and there is an advantage in that it can be purified using a high-performance liquid chromatography method. Furthermore, compared to the conventional low yield of ¹⁸ F-labeled tetrazine or ¹⁸ F-labeled TCO synthesis, the ¹⁸ F-labeled ketone compound of Formula 1 of the present invention can be synthesized from its precursor in a high ¹⁸ F-labeled yield. .