203/212Pb Theranostic Radiopharmaceuticals for Image-guided Radionuclide Therapy for Cancer

doi:10.2174/0929867327999200727190423
摘要

以受体为靶点的图像指导的放射性核素治疗（TRT）被越来越多地认为是一种有前途的癌症治疗方法。特别是，以受体为靶的α粒子疗法的临床潜力作为一种可以改善癌症患者预后的方法受到了广泛关注。为此目的，较高的α粒子（与β粒子相比）的线性能量转移（LET）导致双链DNA断裂的发生率增加，并且局部癌细胞的损害得到改善。最近的临床研究提供了令人信服的证据，表明与β-TRT相比，α-TRT可能具有更强的抗癌作用。发生器产生的212Pb（衰减为α发射体212Bi和212Po）是一种特别有希望的放射性核素，可用于受体靶向的α粒子治疗。将212Pbα-TRT与其他可用放射性核素区分开的第二个吸引人的特征是，可以使用元素匹配的同位素203Pb作为成像替代物来代替治疗性放射性核素。由于无法使用当前的医学扫描仪技术直接进行非侵入式α粒子排放测量，因此成像替代技术可在治疗之前对TRT候选配体的药代动力学和生物分布进行无药理学测定。因此，元素匹配的203Pb标记的放射性药物可用于识别可从212Pbα-TRT中受益的患者，并在治疗前应用适当的剂量和治疗计划。在这篇综述中，我们提供了使用这些同位素进行癌症治疗的简要历史；描述了203 / 212Pb在癌症治疗学中的衰变和化学特性，以及用于生产和纯化这些同位素以用于放射性药物生产的方法学。此外，还提供了医学物理学和剂量学方面的观点，突出了212Pb对于alpha-TRT的潜力以及203Pb替代成像的预期安全性。介绍了最近和当前的临床前和临床研究。本文中发现的结果和提出的观察结果的总和提供了证据，证明203Pb / 212Pb肿瘤治疗药对在癌症的放射药物治疗治疗中具有广阔的应用前景。
关键词: 放射性药物，放射化学，治疗学，铅212，铅203，铅203，铅212，剂量测定法，癌症，放射性核素治疗，SPECT成像，MIRD，基于体素的剂量测定法。
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DOI https://dx.doi.org/10.2174/0929867327999200727190423	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
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