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Thorium chelators for targeted alpha therapy: Rapid chelation of thorium‐226
Author(s) -
Ferrier Maryline G.,
Li Yawen,
Chyan MingKuan,
Wong Roger,
Li Lily,
Spreckelmeyer Sarah,
Hamlin Donald K.,
Mastren Tara,
Fassbender Michael E.,
Orvig Chris,
Wilbur D. Scott
Publication year - 2020
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3875
Subject(s) - chemistry , chelation , ligand (biochemistry) , nuclear chemistry , radiochemistry , thorium , picolinic acid , chelation therapy , inorganic chemistry , organic chemistry , biochemistry , receptor , uranium , metallurgy , materials science
One of the main challenges in targeted alpha therapy is assuring delivery of the α‐particle dose to the targeted cells. Thus, it is critical to identify ligands for α‐emitting radiometals that will form complexes that are very stable, both in vitro and in vivo. In this investigation, thorium‐227 ( t 1/2 = 18.70 days) chelation of ligands containing hydroxypyridinonate (HOPO) or picolinic acid (pa) moieties and the stability of the resultant complexes were studied. Chelation reactions were followed by reversed‐phased HPLC and gamma spectroscopy. Studies revealed that high 227 Th chelation yields could be obtained within 2.5 h or less with ligands containing four Me‐3,2‐HOPO moieties, 1 (83%) and 2 (65%), and also with ligands containing pa moieties, H 4 octapa 3 (65%) and H 4 py4pa 6 (87%). No reaction occurred with H 4 neunpa‐ p ‐Bn‐NO 2 4 , and the chelation reaction with another pa ligand H 4 pypa 5 gave inconsistent yields with a very broad radio‐HPLC peak. The ligands spermine‐(Me‐3,2‐HOPO) 4 1 , H 4 octapa 3 , and H 4 py4pa 6 had high stability (i.e., 87% of 227 Th still bound to the ligand) in phosphate‐buffered saline at room temperature over a 6‐day period. Preliminary studies with ligand 6 demonstrated efficient chelation of thorium‐226 ( t 1/2 = 30.57 min) when heated to 80°C for 5 min.