Assembling and investigating 201Tl radiolabelled texaphyrin nanoparticles targeted to prostate cancer cells for Auger electron radiotherapy
Lead Research Organisation:
King's College London
Department Name: Imaging & Biomedical Engineering
Abstract
"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.
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.
