背景：生物标志物驱动的分子成像已成为癌症精准放射治疗不可或缺的一部分。分子成像探针（包括纳米探针）已在放射治疗成像中得到探索，以精确、无创地监测生物标志物的时空分布，有可能揭示放射治疗过程中的肿瘤杀伤机制和治疗引起的不良反应。方法：我们总结了临床前研究和临床试验的文献报告，主要包括两个部分：1）与放疗相关的临床研究和新兴成像生物标志物，2）分子成像探针在放疗中的作用、功能和可激活机制工作流程。此外，还提出了反思和未来展望。结果：几十年来，人们不断探索许多成像生物标志物，但其中很少有人成功验证其与放射治疗结果和/或放射引起的毒性的相关性。与此同时，针对新兴生物标志物的可激活分子成像探针在动物或小规模人体研究中的精准放射治疗中表现出良好的前景。结论：生物标志物驱动的分子成像探针对于精准放疗至关重要。尽管初步结果非常鼓舞人心，但成像生物标志物的验证和合理的探针设计策略还有待强有力和广泛的研究。特别是，成像生物标志物与放射治疗结果/毒性之间的相关性应通过涉及大量患者的多中心合作来建立。©作者。

Background: Biomarker-driven molecular imaging has emerged as an integral part of cancer precision radiotherapy. The use of molecular imaging probes, including nanoprobes, have been explored in radiotherapy imaging to precisely and noninvasively monitor spatiotemporal distribution of biomarkers, potentially revealing tumor-killing mechanisms and therapy-induced adverse effects during radiation treatment. Methods: We summarized literature reports from preclinical studies and clinical trials, which cover two main parts: 1) Clinically-investigated and emerging imaging biomarkers associated with radiotherapy, and 2) instrumental roles, functions, and activatable mechanisms of molecular imaging probes in the radiotherapy workflow. In addition, reflection and future perspectives are proposed. Results: Numerous imaging biomarkers have been continuously explored in decades, while few of them have been successfully validated for their correlation with radiotherapeutic outcomes and/or radiation-induced toxicities. Meanwhile, activatable molecular imaging probes towards the emerging biomarkers have exhibited to be promising in animal or small-scale human studies for precision radiotherapy. Conclusion: Biomarker-driven molecular imaging probes are essential for precision radiotherapy. Despite very inspiring preliminary results, validation of imaging biomarkers and rational design strategies of probes await robust and extensive investigations. Especially, the correlation between imaging biomarkers and radiotherapeutic outcomes/toxicities should be established through multi-center collaboration involving a large cohort of patients.© The author(s).