Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Molecules. 2022 Aug 4;27(15):4959. doi: 10.3390/molecules27154959.
Radioligand therapy (RLT) is an emergent drug class for cancer treatment. The dose administered to cancer patients is constrained by the radiation exposure to normal tissues to maintain an appropriate therapeutic index. When a radiopharmaceutical or its radiometabolite is retained in the kidneys, radiation dose deposition in the kidneys can become a dose-limiting factor. A good exemplar is [Lu]Lu-DOTATATE, where patients receive a co-infusion of basic amino acids for nephroprotection. Besides peptides, there are other classes of targeting vectors like antibody fragments, antibody mimetics, peptidomimetics, and small molecules that clear through the renal pathway. In this review, we will review established and emerging strategies that can be used to mitigate radiation-induced nephrotoxicity, with a focus on the development and incorporation of cleavable linkers for radiopharmaceutical designs. Finally, we offer our perspectives on cleavable linkers for RLT, highlighting future areas of research that will help advance the technology.
放射性配体治疗（RLT）是一种新兴的癌症治疗药物类别。为了维持适当的治疗指数，给予癌症患者的剂量受到正常组织辐射暴露的限制。当放射性药物或其放射性代谢物在肾脏中滞留时，肾脏中的辐射剂量沉积可能成为剂量限制因素。[Lu]Lu-DOTATATE 就是一个很好的例子，患者接受基础氨基酸的联合输注以进行肾保护。除了肽类，还有其他类别的靶向载体，如抗体片段、抗体模拟物、肽模拟物和小分子，它们通过肾脏途径清除。在这篇综述中，我们将回顾可用于减轻放射性肾毒性的既定和新兴策略，重点介绍用于放射性药物设计的可切割连接物的开发和应用。最后，我们对 RLT 的可切割连接物提出了看法，强调了有助于推动该技术发展的未来研究领域。
