Bringing Capacity for Theranostic Dosimetry Planning to the Nuclear Medicine Clinic

为核医学诊所带来治疗诊断剂量测定规划的能力

• 批准号: 10165668
• 负责人: YUNI K DEWARAJA
• 金额: $ 60.72万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10165668
• 关键词: Clinic; Clinical; Clinical Protocols; Code; Collaborations; Computer software; Development; Discipline of Nuclear Medicine; Dose; Ensure; Environment; FOLH1 gene; Foundations; Future; Image; Image Analysis; Imaging Device; Investigation; Kidney; Label; Learning; Lesion; Malignant Neoplasms; Malignant neoplasm of prostate; Medical Imaging; Methods; Modeling; Neuroendocrine Tumors; Organ; Outcome; Patient-Focused Outcomes; Patients; Peptide Receptor; Procedures; Protocols documentation; Public Health; Radiation therapy; Radioisotopes; Radiolabeled; Radionuclide therapy; Recording of previous events; Reproducibility; Risk; Software Validation; Standardization; Survival Rate; System; Test Result; Testing; Therapeutic Effect; Therapy Clinical Trials; Time; Toxic effect; Translating; Weight; X-Ray Computed Tomography; base; clinical practice; clinical translation; cytotoxic radiation; data handling; design; dosimetry; experience; imaging Segmentation; imaging biomarker; improved; individualized medicine; industry partner; innovation; novel; personalized approach; predictive modeling; prospective; radioligand; radiomics; reconstruction; response; single photon emission computed tomography; standard of care; targeted agent; theranostics; tool; treatment planning; tumor; verification and validation

Abstract Internally administered targeted radionuclide therapy (TRT) with radio-labeled molecules that deliver cytotoxic radiation to tumor has been successfully used to treat multiple cancers. Despite promising results, there is much room to improve the durable response and survival rates achieved with TRT. TRT is ideally suited for the theranostic approach to treatment because emission imaging performed before initiating a treatment cycle can be used to predict the absorbed doses (ADs) that will be delivered. Thus, the activity needed for a therapeutic effect on tumor while keeping critical organ toxicities at an acceptable level can be planned on an individualized basis. While precise treatment planning is routinely used in external beam radiotherapy, in TRT however, treatment with fixed or weight-based activities without consideration of delivered ADs continues to be the standard of care. The main barrier to dosimetry guided personalization of TRT is the lack of dosimetry tools that are valid yet practical for the clinic environment. To improve this situation the objective is to develop, validate and bring to the clinic a platform for patient-specific dosimetry-driven treatment planning that is practical for clinical use and adaptable to various TRTs. The proposed system will integrate a toolbox for SPECT/CT imaging based voxel-level dosimetry with end-to-end testing (Aim 1), validated protocols for reducing the imaging burden associated with patient specific dosimetry (Aim 2), robust dose – outcome models that include clinical factors and imaging biomarkers as covariates (Aim 2), and an interactive user interface that the clinician can use to plan the therapy considering dosimetric and clinical factors and the resulting efficacy/toxicity trade-off (Aim 3). The system integrates new components that will be developed exploiting recent advances such as learning-based methods for low-count SPECT reconstruction and efficient image segmentation atop our existing foundation that includes a previously developed fast Monte Carlo dosimetry code. The collaboration with an industry partner with a track record in translating innovative tools for medical image analysis will help ensure clinical translation of the system. To demonstrate the capacity of the tools developed, patient studies will focus on 177Lu DOTATATE treatment of neuroendocrine tumors. This recently approved therapy is administered in four cycles with fixed activity although there is a unique opportunity to perform SPECT imaging-based lesion/organ dosimetry after each cycle to plan the next cycle. The system can be adapted to therapies with other radionuclides and targeting agents that can benefit from SPECT/CT imaging based planning such as radioligand therapy with 177Lu PSMA for prostate cancer and emerging therapies with alpha emitters. The proposed system integrates adaptations of tools developed in the past by both teams and new tools to bring a new capacity to the end user to effectively plan TRT with all data handling conveniently performed within one platform. This will have a significant positive impact because a personalized dosimetry guided approach to TRT is likely to substantially improve efficacy while maintaining low toxicity, compared with the current arbitrary ‘one dose fits all’ approach.

摘要 使用放射性标记分子进行体内靶向放射性核素治疗（TRT）， 对肿瘤的放射已经成功地用于治疗多种癌症。尽管取得了可喜的成果， TRT的持久缓解率和生存率有待提高。TRT非常适合 因为在开始治疗周期之前进行的发射成像可以 用于预测将输送的吸收剂量（AD）。因此，治疗药物所需的活性 在保持关键器官毒性在可接受水平的同时，可以根据个体化的 基础虽然精确的治疗计划通常用于外射束放射治疗，但是在TRT中， 在不考虑递送AD的情况下进行固定或基于体重的活动治疗仍然是 护理标准。TRT的剂量学指导的个体化的主要障碍是缺乏剂量学工具， 对于临床环境是有效而实用的。为了改善这种情况，目标是开发、验证 并为临床带来一个平台，用于患者特异性剂量测定驱动的治疗计划， 临床使用，适用于各种TRT。所提出的系统将集成SPECT/CT成像工具箱 基于体素水平的剂量测定和端到端测试（目标1），经验证的方案可减少成像负担 与患者特异性剂量测定相关（目标2），包括临床因素的稳健剂量结局模型 和成像生物标志物作为协变量（目标2），以及临床医生可以使用的交互式用户界面， 考虑剂量测定和临床因素的治疗以及由此产生的疗效/毒性权衡（目标3）。的 系统集成了新的组件，这些组件将利用最新的进展（如基于学习的 在我们现有的基础上， 包括以前开发的快速蒙特卡罗剂量测定代码。与行业合作伙伴的合作， 在翻译用于医学图像分析的创新工具方面的跟踪记录将有助于确保 系统为了证明所开发工具的能力，患者研究将集中在177 Lu DOTATATE上。 神经内分泌肿瘤的治疗。这种最近批准的治疗是在四个周期与固定的 活动，虽然有一个独特的机会进行SPECT成像为基础的病变/器官剂量测定后， 每一个周期都要计划下一个周期。该系统可以适用于其他放射性核素和靶向治疗 可从基于SPECT/CT成像的计划中获益的药物，如177 Lu PSMA放射性配体治疗 用于前列腺癌和使用α发射体的新兴疗法。拟议的系统集成了以下方面的调整： 两个团队过去开发的工具和新工具，为最终用户带来新的能力， 计划TRT，所有数据处理在一个平台内方便地执行。这将产生重大的积极影响 影响，因为TRT的个性化剂量测定指导方法可能会大大提高疗效， 保持低毒性，与目前任意的“一剂适合所有”的方法相比。