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: 9973682
• 负责人: YUNI K DEWARAJA
• 金额: $ 60.31万
• 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/9973682
• 关键词: Clinic; Clinical; Clinical Protocols; Code; Collaborations; Computer software; Data; 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; 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.

抽象的 使用可提供细胞毒性的放射性标记分子进行内部靶向放射性核素治疗 (TRT) 肿瘤放射已成功用于治疗多种癌症。尽管结果令人鼓舞，但还有很多 提高 TRT 的持久反应和存活率的空间。 TRT 非常适合 治疗诊断方法，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，治疗所需的活性 可以根据个体化方案规划对肿瘤的影响，同时将关键器官毒性保持在可接受的水平 基础。虽然精确的治疗计划通常用于外照射放射治疗，但在 TRT 中， 不考虑所提供的 AD 的固定或基于体重的活动治疗仍然是 护理标准。剂量测定引导 TRT 个性化的主要障碍是缺乏剂量测定工具 对于临床环境来说是有效且实用的。为了改善这种情况，目标是开发、验证 并为诊所带来一个针对患者特定剂量测定驱动的治疗计划的平台，该平台对于 临床使用并适应各种TRT。拟议的系统将集成 SPECT/CT 成像工具箱 基于体素级剂量测定和端到端测试（目标 1），经过验证的协议可减轻成像负担 与患者特定剂量测定（目标 2）相关，包括临床因素的稳健剂量结果模型 和成像生物标志物作为协变量（目标 2），以及临床医生可以用来制定计划的交互式用户界面 治疗考虑剂量测定和临床因素以及由此产生的功效/毒性权衡（目标 3）。这 系统集成了新的组件，这些组件将利用最新的进步（例如基于学习的 在我们现有的基础上进行低计数 SPECT 重建和高效图像分割的方法 包括先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 翻译医学图像分析创新工具的记录将有助于确保临床翻译 系统。为了证明所开发工具的能力，患者研究将重点关注 177Lu DOTATATE 神经内分泌肿瘤的治疗。这种最近批准的疗法分四个周期进行，固定 活动，尽管在之后有一个独特的机会进行基于 SPECT 成像的病变/器官剂量测定 每个周期都计划下一个周期。该系统可以适应其他放射性核素和靶向治疗 可以受益于基于 SPECT/CT 成像的规划的药物，例如使用 177Lu PSMA 的放射性配体治疗 用于前列腺癌和阿尔法发射体的新兴疗法。所提议的系统集成了以下适应性： 团队过去开发的工具和新工具可以为最终用户带来新的能力，从而有效地 规划 TRT，并在一个平台内方便地执行所有数据处理。这将产生显着的积极作用 影响，因为个性化剂量测定引导的 TRT 方法可能会显着提高疗效，同时 与目前任意的“一剂适用所有”方法相比，保持低毒性。