Synthesis and radiolabeling of a polar [125I]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 (I-125) 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 degrees 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.

Automated summary

Pretargeting imaging has gained attention for its excellent bioorthogonality and improved imaging contrast compared to conventional imaging. A new iodo tetrazine derivative has been synthesized and developed into an iodine-125 analog. Radiolabeling with N-chlorosuccinimide or chloramine-T in MeCN or MeOH resulted in a radiochemical conversion of >80%. Deprotection was successful when the radiolabeled tetrazine was stirred in 6-M HCl(aq.) at 60 degrees C for 2.5 h. This is the first iodine-labeled H-tetrazine. In vivo investigations on its pretargeting ability are currently underway.