APPLICATIONS OF TECHNOLOGY:
- Development of radiopharmaceuticals for cancer diagnosis and treatment
- Development of antibodies labeled with radionuclides
- Simplified synthesis compared to other structures
- Faster radiolabeling at room temperature
- Formation of highly stable radiometal complexes
- Higher synthetic yields
Thorium-227 (227Th) is an alpha-particle emitting radioactive isotope that shows high therapeutic potential for treating tumors such as those expressing mesothelin. The current state of the art ligand used for the chelation of 227Th and radiolabeling of biological molecules is an octadentate ligand that shows promising clinical results. However, its broader applications are limited by its challenging, multistep synthesis. Therefore, it is important to develop alternative ligands that are more synthetically accessible in order to further develop the use of 227Th within radiopharmaceuticals for targeted alpha therapy.
Scientists at Berkeley Lab have developed a new ligand that can bind to radiometals and allow for radiolabeling of biomolecules in cancer treatment. This new ligand, called DOTHOPO, is able to rapidly bind 227Th, as well as other radioisotopes, even at low concentrations and form highly stable complexes. Serum stability and biodistribution experiments were able to confirm that the ligand possesses excellent in vitro and in vivo stability. Parallel experiments were conducted with Zirconium-89 (89Zr), a common radionuclide used in positron emission tomography, to demonstrate that DOTHOPO is also effective in forming stable in vivo complexes with this radionuclide. Additionally, DOTHOPO can be chemically modified to enable radiolabeling of peptides and antibodies.
This new ligand can be synthesized in a small number of steps from readily available materials, making it more synthetically accessible than state of the art ligands for radiolabeling.
Proof of concept
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