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) analog (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, among 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.