title: An efficient chelator for complexation of thorium-227.
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.
authors.affiliation: The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ramdahl
authors.affiliation: The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway.
authors.forename: Hanne T
authors.initials: HT
authors.lastname: Bonge-Hansen
authors.affiliation: The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway.
authors.forename: Olav B
authors.initials: OB
authors.lastname: Ryan
authors.affiliation: The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway.
authors.forename: Smund
authors.initials: S
authors.lastname: Larsen
authors.affiliation: Synthetica AS, Gaustadalléen 21, 0349 Oslo, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Herstad
authors.affiliation: Synthetica AS, Gaustadalléen 21, 0349 Oslo, Norway.
authors.forename: Marcel
authors.initials: M
authors.lastname: Sandberg
authors.affiliation: The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Bjerke
authors.affiliation: The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway.
authors.forename: Derek
authors.initials: D
authors.lastname: Grant
authors.affiliation: The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Brevik
authors.affiliation: The Department of Thorium Research, Bayer AS, Drammensveien 288, 0283 Oslo, Norway. Electronic address: alan.cuthbertson@bayer.com.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Cuthbertson
mesh_terms: D000818:Animals; D001572:Benzofurans; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects; D007554:Isotopes; D008168:Lung / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D011804:Quinolines; D013910:Thorium / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C576715:(3aS,4S,9bS)-N-(2-(8-cyano-1-formyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo(3,2-c)quinolin-4-yl)-2-methylpropyl)-4,6-difluorobenzofuran-2-carboxyamide; D001572:Benzofurans; D002614:Chelating Agents; D007554:Isotopes; D011804:Quinolines; D013910:Thorium
keywords: 3-hydroxy-N-methyl-2-pyridinone; Chelator; Me-3,2-HOPO; Targeted Thorium Conjugates (TTCs); Thorium-227 (Th-227)