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

“MRC：Katarzyna Osytek：MR/N013700/1”靶向放射性核素疗法是一种新兴的非常有前景的癌症治疗策略，177Lu-DOTATE治疗神经内分泌肿瘤以及最近用177Lu-PSMA-617和225Ac-PSMA-617治疗转移性前列腺癌的临床成功证明了这一点。然而，177Lu发射的β粒子也有缺点，特别是它们的射程很长(几毫米)，导致对非靶向正常细胞的照射和毒性，以及非常低的LET(0.1-1kev/um)，这限制了它们的细胞毒作用。像225Ac这样的阿尔法粒子发射器的射程要短得多，范围在50-100微米，而LET(50-230电子伏安/微米)更高，这使得它们对杀死癌细胞非常有效和有选择性。但阿尔法粒子放射治疗的一个主要限制是放射性核素会衰变成放射性的子产物，可能会重新分布到正常组织并造成毒性。俄歇电子能谱与阿尔法粒子相似，因为它们的射程很短(~lt；1um)，LET很高(4-26kev/um)，对杀死癌细胞是有效的，但重要的是，发射出的AE放射性核素会衰变成稳定的子产物。201Tl是癌症治疗中最具吸引力的AE发射体之一，因为每次衰变都会释放出高丰度的AEs。在我在多伦多大学的研究提案中，我将通过探索一种新的策略来传递这种放射性核素，从而解决将201Tl具体输送到癌细胞中的挑战，方法是使用与201Tl复合的靶向纹状体蛋白纳米颗粒。

"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.