Sgouros George, Hobbs Robert F, Abou Diane S
From the Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD.
Am Soc Clin Oncol Educ Book. 2014:e121-5. doi: 10.14694/EdBook_AM.2014.34.e121.
Radiopharmaceutical therapy (RPT) is a treatment modality that involves the use of radioactively labeled targeting agents to deliver a cytotoxic dose of radiation to tumor while sparing normal tissue. The biologic function of the target and the biologic action of the targeting agent is largely irrelevant as long as the targeting agent delivers cytotoxic radiation to the tumor. Preclinical RPT studies use imaging and ex vivo evaluation of radioactivity concentration in target and normal tissues to obtain biodistribution and pharmacokinetic data that can be used to evaluate radiation absorbed doses. Since the efficacy and toxicity of RPT depend on radiation absorbed dose, this quantity can be used to translate results from preclinical studies to human studies. The absorbed dose can also be used to customize therapy to account for pharmacokinetic and other differences among patients so as to deliver a prespecified absorbed dose to the tumor or to dose-limiting tissue. The combination of RPT with other agents can be investigated and optimized by identifying the effect of other agents on tumor or normal tissue radiosensitivity and also on how other agents change the absorbed dose to these tissues. RPT is a distinct therapeutic modality whose mechanism of action is well understood. Measurements can be made in preclinical models to help guide clinical implementation of RPT and optimize combination therapy using RPT.
放射性药物治疗（RPT）是一种治疗方式，它涉及使用放射性标记的靶向剂，在 sparing正常组织的同时，向肿瘤输送细胞毒性剂量的辐射。只要靶向剂向肿瘤输送细胞毒性辐射，靶点的生物学功能和靶向剂的生物学作用在很大程度上是无关紧要的。临床前RPT研究使用成像和对靶点及正常组织中放射性浓度的体外评估，以获得可用于评估辐射吸收剂量的生物分布和药代动力学数据。由于RPT的疗效和毒性取决于辐射吸收剂量，这个量可用于将临床前研究结果转化为人体研究结果。吸收剂量还可用于定制治疗，以考虑患者之间的药代动力学和其他差异，从而向肿瘤或剂量限制组织输送预先指定的吸收剂量。通过确定其他药物对肿瘤或正常组织放射敏感性的影响，以及其他药物如何改变这些组织的吸收剂量，可以研究和优化RPT与其他药物的联合使用。RPT是一种独特的治疗方式，其作用机制已得到充分理解。可以在临床前模型中进行测量，以帮助指导RPT的临床实施，并优化使用RPT的联合治疗。
