Alpha Radionuclide Therapy Using Polymeric Nanocarriers: Solution to the Recoil Problem?

In radionuclide therapy, radioisotopes are used to irradiate tumours from within the body. Usually beta-emitters coupled to tumour-targeting molecules are used, which specifically accumulate at the tumour site. Instead of using beta-emitters, it is also possible to use radionuclides which emit an alpha particle upon decay. Alpha particles have a shorter range and are much more effective in destroying tumour cells. Alpha radionuclide therapy is steadily gaining interest, although currently in most studies radionuclides with relatively short half-life are used. Long lived radionuclides like the 225Ac employed in this thesis are ideal for the treatment of tumours which take a longer time to reach. The long halflife of 225Ac combined with four alpha particles in its decay chain ensure long irradiation of the targeted tissue. However, upon alpha-decay the daughter nuclide receives a recoil energy decoupling it from any targeting agent, allowing it to diffuse throughout the body to irradiate healthy tissue. The main goal of this thesis is to develop polymeric nanocarriers, so-called polymersomes, which retain the recoiling daughter atoms of 225Ac in order to limit healthy tissue toxicity in alpha radionuclide therapy.