Synthesis and radiolabeling of a polar [125 I]I-1,2,4,5-tetrazine

  • J Labelled Comp Radiopharm. 2023 Jan;66(1):22-30. doi: 10.1002/jlcr.4009.
Natasha Bidesi  1 ,  Vladimir Shalgunov  1  2 ,  Umberto Maria Battisti  1 ,  Lars Hvass  3 ,  Jesper Tranekjaer Jørgensen  3 ,  Christian B M Poulie  1 ,  Andreas I Jensen  4 ,  Andreas Kjaer  3 ,  Matthias M Herth  1  2
Affiliations
  • 1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • 2. Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen, Denmark.
  • 3. Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • 4. Center for Nuclear Technologies (DTU Nutech), Technical University of Denmark (DTU), Roskilde, Denmark.
PMID: 36539610 DOI: 10.1002/jlcr.4009
Abstract

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.

Keywords
bioorthogonal; click chemistry; idodine-125; pretargeting; tetrazine.
Products