Department of Radiology, University of British Columbia, Vancouver, Canada.
Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, Canada.
Theranostics. 2024 May 27;14(9):3404-3422. doi: 10.7150/thno.93973. eCollection 2024.
Radiopharmaceutical therapy (RPT) is a rapidly developing field of nuclear medicine, with several RPTs already well established in the treatment of several different types of cancers. However, the current approaches to RPTs often follow a somewhat inflexible "one size fits all" paradigm, where patients are administered the same amount of radioactivity per cycle regardless of their individual characteristics and features. This approach fails to consider inter-patient variations in radiopharmacokinetics, radiation biology, and immunological factors, which can significantly impact treatment outcomes. To address this limitation, we propose the development of theranostic digital twins (TDTs) to personalize RPTs based on actual patient data. Our proposed roadmap outlines the steps needed to create and refine TDTs that can optimize radiation dose to tumors while minimizing toxicity to organs at risk. The TDT models incorporate physiologically-based radiopharmacokinetic (PBRPK) models, which are additionally linked to a radiobiological optimizer and an immunological modulator, taking into account factors that influence RPT response. By using TDT models, we envisage the ability to perform virtual clinical trials, selecting therapies towards improved treatment outcomes while minimizing risks associated with secondary effects. This framework could empower practitioners to ultimately develop tailored RPT solutions for subgroups and individual patients, thus improving the precision, accuracy, and efficacy of treatments while minimizing risks to patients. By incorporating TDT models into RPTs, we can pave the way for a new era of precision medicine in cancer treatment
放射性药物治疗(RPT)是核医学领域的一个快速发展领域,已有几种 RPT 方法成功应用于多种不同类型癌症的治疗。然而,目前的 RPT 方法通常遵循一种相对僵化的“一刀切”模式,即无论患者的个体特征和表现如何,每个周期都给予相同数量的放射性活性。这种方法未能考虑放射性药代动力学、辐射生物学和免疫因素在患者间的差异,而这些因素可能会显著影响治疗效果。为了解决这一局限性,我们提出开发治疗性数字孪生体(TDT),根据实际患者数据来个性化 RPT。我们提出的路线图概述了创建和完善 TDT 的步骤,这些 TDT 可以优化肿瘤的放射剂量,同时最大限度地降低对风险器官的毒性。TDT 模型纳入了基于生理学的放射性药物动力学(PBRPK)模型,这些模型还与放射生物学优化器和免疫调节剂相连接,考虑到影响 RPT 反应的因素。通过使用 TDT 模型,我们设想能够进行虚拟临床试验,选择能够改善治疗效果同时降低与二次效应相关风险的治疗方法。该框架可以使临床医生能够最终为亚组和个体患者开发定制的 RPT 解决方案,从而提高治疗的精准度、准确性和疗效,同时降低患者的风险。通过将 TDT 模型纳入 RPT,我们可以为癌症治疗的精准医学新时代铺平道路。
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