Targeted alpha therapy (TAT) is a growing field that has potential in treatment of diseases, such as cancer micrometastases and viral- or bacterial-related diseases. The use of α-emitting radionuclides in pharmaceuticals can achieve effective therapeutic results due to the short path length and high potency of the α particle. This approach focuses all destructive power to a small targeted area while minimizing damage to surrounding normal tissues, unlike β-emitting radionuclides having longer ranges. Amongst α-emitting radionuclides 226Th (t1/2 = 30.57 min) has been mentioned as a possible candidate for TAT. To the best of our knowledge no 226Th labeling results have been reported yet. But to alleviate 226Th short half-life, chemistry can be performed with a longer-lived thorium isotope such as 227Th (t1/2 = 18.68 d). Interestingly, 227Th being the direct parent of 223Ra is considered as a good candidate for TAT as well. Recent studies showed that ligands containing hydroxypyridinonate (HOPO) moieties (i.e., 1,2-or Me-3,2-HOPO) and some derivatives have demonstrated high radiolabeling yields with thorium. A different class of ligand, built around the picolinic acid functional moiety, has been studied with zirconium (believed to be a good surrogate for thorium) showed great promises. In this study, we evaluated radiolabeling yields and stability of chelated thorium for some home-made HOPO and picolinic acid ligands using 227Th. In order to simulate radiolabeling conditions required with 226Th, a short reaction time of 10 min was investigated, and aliquots of reaction mixture were analyzed by HPLC. Longer reaction times were used to allow systems to reach equilibrium, and analyses were performed to compare the radiochemical labeling yield between ligands. Finally, ligands with the highest labeling yields were reacted with higher quantities of 227Th, to accommodate 14 days study, then the radiolabeled compound was isolated and studied by HPLC and gamma spectroscopy for stability in phosphate buffered saline (PBS) solution at room temperature.

Evaluation of thorium chelators for targeted alpha therapy application

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.