University of California at Davis, Davis, California.
NIH/NCI, Bethesda, Maryland.
J Nucl Med. 2021 Aug 1;62(8):1133-1139. doi: 10.2967/jnumed.120.255547. Epub 2020 Dec 4.
In 2018, the National Cancer Institute and NRG Oncology partnered for the first time to host a joint workshop on systemic radiopharmaceutical therapy (RPT) to specifically address dosimetry issues and strategies for future clinical trials. The workshop focused on current dosimetric approaches for clinical trials, strategies under development that would optimize dose reporting, and future desired or optimized approaches for novel emerging radionuclides and carriers in development. In this article, we review the main approaches that are applied clinically to calculate the absorbed dose. These include absorbed doses calculated over a variety of spatial scales, including whole body, organ, suborgan, and voxel, the last 3 of which are achievable within the MIRD schema (S value) and can be calculated with analytic methods or Monte Carlo methods, the latter in most circumstances. This article will also contrast currently available methods and tools with those used in the past, to propose a pathway whereby dosimetry helps the field by optimizing the biologic effect of the treatment and trial design in the drug approval process to reduce financial and logistical costs. We also briefly discuss the dosimetric equivalent of biomarkers to help bring a precision medicine approach to RPT implementation when merited by evidence collected during early-phase trial investigations. Advances in the methodology and related tools have made dosimetry the optimum biomarker for RPT.
2018 年,美国国家癌症研究所(National Cancer Institute)和 NRG 肿瘤学首次合作举办了一场关于全身放射性药物治疗(RPT)的联合研讨会,专门讨论剂量学问题和未来临床试验的策略。该研讨会重点关注临床试验中的当前剂量学方法、正在开发的将剂量报告最优化的策略,以及新出现的放射性核素和载体在开发中的未来所需或优化的方法。在本文中,我们回顾了临床上应用于计算吸收剂量的主要方法。这些方法包括在多种空间尺度上计算的吸收剂量,包括全身、器官、亚器官和体素,后 3 种方法在 MIRD 方案(S 值)内是可行的,可以用分析方法或蒙特卡罗方法计算,在后一种情况下更为常见。本文还将目前可用的方法和工具与过去使用的方法和工具进行对比,提出了一种途径,即通过优化治疗和试验设计的生物学效应,在药物审批过程中帮助剂量学领域,从而降低财务和后勤成本。我们还简要讨论了与剂量学等效的生物标志物,以在早期试验研究中收集到的证据证明合理的情况下,为放射性药物治疗的实施带来精准医学方法。方法学和相关工具的进步使剂量学成为放射性药物治疗的最佳生物标志物。