Beyond DOTA: A New and Improved Chelating Agent

Targeted radiotherapy is increasingly used in cancer treatment with many of the most important radionuclides being those of large metals capable of emitting alpha radiation. When alpha emitting radionuclides are conjugated to a targeting element e.g. peptide, mono-clonal antibody or small molecule, they are highly specific and effective at killing target cells. However, developing new targeted alpha therapy (TAT) agents has been limited by the high lability of the large metal ions when complexed with traditional chelating ligands. UVic has addressed this challenge by developing an advanced boron-capped chelating agent capable of encapsulating very large metal ions with improved stability. In addition to large metal ions, the cage can bind other metals such as the lanthanides. The ability to bind multiple metals concurrently allows for this novel chelating agent to be used for both diagnostics and imaging; it is the next step for targeted radiotherapy applications in healthcare.

Researchers at the University of Victoria have developed a novel clathrochelate (cage) capable of binding metals, including heavy metals for use in nuclear medicine. When coupled with chemical linkers and targeting biomolecules the metal-complexing cage has the potential to specifically and effectively kill target cells. The cage has the added benefit of three biomolecule binding sides to improve conjugation efficiency and help target specific locations in the body.

Preparation of the cage and loading of metals is quick and easy. The rapid kinetics allow metals to be taken up in seconds to minutes plus unlike DOTA, a common chelating agent used in medical imaging and radiopharmaceuticals, UVic’s cage can uptake metals at room temperature. This is a huge advantage to those using targeting biomolecules which are heat sensitive or looking for improved safety since the radioactive agent can be added at the end of manufacturing.

The versatile, stable cage can bind multiple metals at one time making it ideal for radio-theranostics. Additionally, the cage preferentially binds large and highly charged ions with high thermodynamic stability and low lability with metals such as lanthanides and barium making this technology ideal for nuclear therapeutic applications. 

Cancer immunotherapy, including:

• delivery of large radionuclides, including α-emitters,
• theranostics,
• diagnostics & imaging.