Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Chemistry, University of Missouri, Columbia, Missouri.
J Nucl Med. 2022 Nov;63(11):1636-1641. doi: 10.2967/jnumed.122.264373. Epub 2022 Sep 2.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer care, but many patients with poorly immunogenic tumors fail to benefit. Preclinical studies have shown that external beam radiotherapy (EBRT) can synergize with ICI to prompt remarkable tumor regression and even eradication. However, EBRT is poorly suited to widely disseminated disease. Targeted radiopharmaceutical therapy (TRT) selectively delivers radiation to both the primary tumor and the metastatic sites, and promising results achieved with this approach have led to regulatory approval of certain agents (e.g., Lu-PSMA-617/Pluvicto for metastatic prostate cancer). To further improve therapeutic outcomes, combining TRT and ICI is a burgeoning research area, both preclinically and in clinical trials. Here we introduce basic TRT radiobiology and survey emerging and clinically translated TRT agents that have been combined with ICI.
免疫检查点抑制剂 (ICIs) 彻底改变了癌症治疗方式，但许多免疫原性较差的肿瘤患者并未从中获益。临床前研究表明，外部束放射治疗 (EBRT) 可与 ICI 协同作用，促使肿瘤显著消退甚至消除。然而，EBRT 不太适用于广泛播散的疾病。靶向放射性药物治疗 (TRT) 可选择性地将辐射传递至原发肿瘤和转移部位，该方法取得的有前景的结果已促使某些药物获得监管批准（例如，Lu-PSMA-617/Pluvicto 用于转移性前列腺癌）。为了进一步提高治疗效果，TRT 和 ICI 的联合应用是一个迅速发展的研究领域，包括临床前和临床试验。本文介绍了基本的 TRT 放射生物学，并综述了与 ICI 联合应用的新兴和已临床转化的 TRT 药物。
