Synthesis and Radiolabeling of a polar [¹²⁵ I]I-1,2,4,5-Tetrazine

Pretargeting imaging has gained a lot of prominence, due to its excellent bioorthogonality and improved imaging contrast compared to conventional imaging. A new iodo tetrazine (Tz) derivative has been synthesized and further developed into the corresponding iodine-125 (¹²⁵ I) analogue (12), via the trimethylstannane precursor. Radiolabeling with either N-chlorosuccinimide or chloramine-T, in either MeCN or MeOH proceeded with a radiochemical conversion (RCC) of >80 %. Subsequent deprotection only proved successful, amongst the tested conditions, when the radiolabeled Tz was stirred in 6 M HCl(_aq.) at 60 ° C for 2.5 h. To the best of our knowledge this is the first H-tetrazine labeled with Iodine. In vivo investigations on the pretargeting ability of 12 are currently under way.