Details

Autor(en) / Beteiligte

• Ferrier, Maryline G.
• Li, Yawen
• Chyan, Ming‐Kuan
• Wong, Roger
• Li, Lily
• Spreckelmeyer, Sarah
• Hamlin, Donald K.
• Mastren, Tara
• Fassbender, Michael E.
• Orvig, Chris
• Wilbur, D. Scott

Titel

Thorium chelators for targeted alpha therapy: Rapid chelation of thorium‐226

Ist Teil von

• Journal of labelled compounds & radiopharmaceuticals, 2020-10, Vol.63 (12), p.502-516

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (t1/2 = 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 227Th 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, H4octapa 3 (65%) and H4py4pa 6 (87%). No reaction occurred with H4neunpa‐p‐Bn‐NO2 4, and the chelation reaction with another pa ligand H4pypa 5 gave inconsistent yields with a very broad radio‐HPLC peak. The ligands spermine‐(Me‐3,2‐HOPO)4 1, H4octapa 3, and H4py4pa 6 had high stability (i.e., 87% of 227Th 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 (t1/2 = 30.57 min) when heated to 80°C for 5 min. Tetra‐HOPO, ligand 1, and H4octapa, ligand 3, provided fast labeling and good yields under mild reaction conditions H4py4pa, ligand 6, appeared to offer higher stability than ligand 3, although it required microwave reaction at high temperature to achieve high labeling yield within 10 min Rapid and high yielding chelation of 226Th from a 230U/226Th generator was demonstrated using microwave heating