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

“MRC：Katarzyna Osytek：MR/N 013700/1“靶向放射性核素治疗是一种新兴的、非常有前途的癌症治疗策略，177 Lu-DOTATATE治疗神经内分泌肿瘤以及最近177 Lu-PSMA-617和225 Ac-PSMA-617治疗转移性前列腺癌的临床成功证明了这一点。然而，由177 Lu发射的β粒子具有缺点，特别是它们的长射程（几毫米），这导致对非靶向正常细胞的辐射和毒性，以及它们非常低的LET（0.1-1 keV/um），这限制了它们的细胞毒性效力。诸如225 Ac的α粒子发射体具有50-100 μ m的短得多的射程和更高的LET（50-230 keV/μ m），这使得它们对于杀死癌细胞非常有效和选择性。但是α粒子放射治疗的一个主要限制是放射性核素衰变为放射性子产物，这些子产物可以重新分布到正常组织并引起毒性。AE类似于α粒子，因为它们具有非常短的射程（<1 μ m）和高LET（4-26 keV/μ m），并且能够杀死癌细胞，但重要的是，AE发射放射性核素衰变为稳定的子产物。201 Tl是用于癌症治疗的最有吸引力的AE发射体之一，这是由于每次衰变发射的AE的高丰度。我将在多伦多大学的研究计划中，通过探索一种新的策略，使用复合201 Tl的靶向德克萨卟啉纳米颗粒来递送这种放射性核素，来解决将201 Tl特异性递送到癌细胞中的挑战。

"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.