Development of targeted 161Tb-radiolabeled nanoparticles

Objectives: Currently applied cancer therapeutic strategies focus on the non-specific destruction of cells showing uncontrolled growth. This implies that rapidly dividing noncancerous cells may also be damaged. However, there is now a greater emphasis on targeted radionuclide therapies that are designed to damage only the targeted cells. Out of the suitable therapeutic radionuclides, Terbium-161 is gathering more interest in recent years because of its favorable decay properties. It has a half-life of 6.9 days and decays via emission of –-particles (average energy of 154 keV) which have a maximum tissue range of 0.29 mm and linear energy transfer (LET) around 0.32 keV/mm. Additionally, Terbium-161 releases Auger/ conversion electrons during decay, leading to a much higher dose being delivered locally compared to Lutetium-177 which possesses similar decay characteristics but does not emit Auger/conversion electrons. The simultaneous emission of -rays makes Terbium-161 a high-potential theranostic radionuclide. Radionuclides are traditionally transported to the tumor by the means of a chelating molecule coupled to a targeting vector. However, trans-chelation may occur, leading to the potential release of free radionuclides in the organism and hence to the accumulation in non-targeted organs. Furthermore, the dose accumulated in the tumor may be relatively low because of the fast renal clearance of such therapeutic agents. Targeted nano- particles containing the theranostic radionuclide Terbium-161 are thus being developed to address these issues. Methods: Our work focuses on synthesizing core-shell nanoparticles via thermal decomposition of lanthanide salts, their silanization, functionalization with a targeting vector, and finally their characterization. Results: Results show that core-shell NaGdF4@NaGdF4:Tb3+ nano-particles could be produced with a size around 16 nm with a silica coating thickness in the order of a few nanometers. We also showed that modified folic acid could be easily coupled to the surface of silica-coated nanoparticles through the use of the so-called “thiolclick” chemistry. Conclusions: The synthesis involving [161Tb]Tb-doped nanoparticles is currently being carried out to investigate their radiochemical behavior (yield and stability).