Assembling and investigating 201Tl radiolabelled texaphyrin nanoparticles targeted to prostate cancer cells for Auger electron radiotherapy

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"MRC : Katarzyna Osytek : MR/N013700/1"Targeted radionuclide therapy is an emerging and very promising strategy for cancer treatment, as evidenced by the proven clinical success in treating neuroendocrine tumours with 177Lu-DOTATATE and more recently, metastatic prostate cancer with 177Lu-PSMA-617 and 225Ac-PSMA-617. However, beta-particles emitted by 177Lu have disadvantages, particularly their long range (several millimeters) which results in irradiation and toxicity to non-targeted normal cells, as well as their very low LET (0.1-1 keV/um), which limits their cytotoxic potency. Alpha-particle emitters such as 225Ac have a much shorter range of 50-100 um and higher LET (50-230 keV/um) which makes them very potent and selective for killing cancer cells. But a major limitation to alpha-particle radiotherapy is that the radionuclides decay to radioactive daughter products, which can redistribute to normal tissues and cause toxicity. AEs are analogous to alpha-particles in that they have a very short range (<1um) and high LET (4-26 keV/um) and are potent for killing cancer cells, but importantly, AE-emitting radionuclides decay to a stable daughter product. 201Tl is one of the most attractive AE emitters for cancer therapy due to the high abundance of AEs emitted per decay. I will address the challenge of specifically delivering 201Tl into cancer cells in my research proposal at the University of Toronto by exploring a new strategy to deliver this radionuclide using targeted texaphyrin nanoparticles that complex 201Tl.