2. Academic Validation
  3. An efficient chelator for complexation of thorium-227

An efficient chelator for complexation of thorium-227

  • Bioorg Med Chem Lett. 2016 Sep 1;26(17):4318-21. doi: 10.1016/j.bmcl.2016.07.034.
Thomas Ramdahl 1,  Hanne T Bonge-Hansen 1,  Olav B Ryan 1,  Smund Larsen 1,  Gunnar Herstad 2,  Marcel Sandberg 2,  Roger M Bjerke 1,  Derek Grant 1,  Ellen M Brevik 1,  Alan S Cuthbertson 3
Affiliations

Affiliations

  • 1 The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway.
  • 2 Synthetica AS, Gaustadalléen 21, 0349 Oslo, Norway.
  • 3 The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway. Electronic address: [email protected].
PMID: 27476138 DOI: 10.1016/j.bmcl.2016.07.034
Abstract

We present the synthesis and characterization of a highly efficient thorium chelator, derived from the octadentate hydroxypyridinone class of compounds. The chelator forms extremely stable complexes with fast formation rates in the presence of Th-227 (ambient temperature, 20min). In addition, mouse biodistribution data are provided which indicate rapid hepatobiliary excretion route of the chelator which, together with low bone uptake, supports the stability of the complex in vivo. The carboxylic acid group may be readily activated for conjugation through the ɛ-amino groups of lysine residues in biomolecules such as Antibodies. This chelator is a critical component of a new class of Targeted Thorium Conjugates (TTCs) currently under development in the field of oncology.

Keywords

3-hydroxy-N-methyl-2-pyridinone; Chelator; Me-3,2-HOPO; Targeted Thorium Conjugates (TTCs); Thorium-227 (Th-227).

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