Targeted alpha-therapy (TAT) through composition of biocompatible nanoparticles able to carry Ra-223.

Researchers at the Norwegian University of Science and Technology (NTNU) have made an exciting discovery related to targeted radionuclide therapy, a therapeutic strategy that aims to treat cancer by delivering radiation specifically to tumor cells. The discovery involves a small virus-sized particle (NP) that has a unique ability to bind to and hold a radioactive substance called radium Ra-223. Since the NPs are made of biopolymers that are biocompatible and can be injected into the bloodstream, they can transport the radioactive substance directly to the tumor. This property is unique from existing solutions and could open up new possibilities in targeted alpha therapy. If successful with further studies in mouse models, the project could lead to more effective targeted cancer treatments using radium Ra-223. Continuous work is underway to optimize the NPs and prove their potential, so that Ra-223 can also be used to treat cancers outside the skeleton.

NTNU researchers have developed and further refined a method for manufacturing nanoparticles (NPs) based on biocompatible biopolymer (one which is based on alginate) that can be functionalized on their surface. These NPs can bind Ra-223, an isotope with no effective functional chelator to this end. In this project we have optimized the Ra-binding and stability of the NPs. The selectivity between radium (Ra) and calcium (Ca) in nanoparticles (NPs) and calcium alginate has never been determined. Since non-radioactive Ra isotopes aren't available, we used barium (Ba) as a stand-in. Using equilibrium dialysis, we defined the impact of ion-balance and polymer length within NPs. These results are crucial for creating NP's with optimized Ra-binding. Furthermore, size and NP-compositions was determined (using techniques like SANS, SAXS, SEC-MALLS and static and dynamic light scattering). The most effective NPs with respect to Ra-223 binding were those based on long G-polymers which form NPs around 100 nm in diameter. These sizes were confirmed through AFM. The NPs are developed within this project is now ready for in vivo biodistribution analyses.