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

基本信息

批准号：
10620806
负责人：
YUNI K DEWARAJA
金额：
$ 59.43万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
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/10620806
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 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 absorption 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

项目摘要

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.

抽象的内部施用的靶向放射线疗法（TRT），带有射击标记的分子，可传递细胞毒性对肿瘤的辐射已成功用于治疗多种癌症。尽管有希望的结果，但仍有很多提高TRT实现的耐用响应和存活率的空间。 TRT非常适合治疗方法是因为在启动治疗周期之前进行的排放成像可以用于预测将交付的吸收剂量（AD）。那，治疗所需的活动可以在个性化的同时对肿瘤的影响，同时将关键器官毒性保持在可接受的水平上基础。虽然精确治疗计划通常用于外束放疗中，但在TRT中，未考虑交付的广告的固定或基于体重的活动的治疗仍在护理标准。剂量学指导性个性化的主要障碍是缺乏剂量计的工具对于诊所环境有效但有效。为了改善这种情况，目标是发展，验证并将其带到诊所的平台，以针对患者特定的剂量测定驱动的治疗计划进行实用临床使用，适用于各种TRT。提出的系统将集成一个用于SPECT/CT成像的工具箱基于端到端测试的基于体素级剂量测定（AIM 1），验证了减少成像伯恩的验证协议与患者特定的剂量测定（AIM 2），鲁棒剂量 - 包括临床因素的结果模型相关并成像生物标志物作为协变量（AIM 2），以及临床可以使用的交互式用户界面该治疗考虑了剂量和临床因素以及由此产生的效率/毒性取舍（AIM 3）。系统集成了将开发利用最新进展的新组件，例如基于学习在我们现有的基础上，低计算Spect重建和有效图像分割的方法包括先前开发的快速蒙特卡洛剂量法代码。与行业合作伙伴的合作翻译创新工具进行医学图像分析的往绩将有助于确保临床翻译系统。为了证明开发工具的能力，患者研究将重点放在177lu dotatate上神经内分泌肿瘤的治疗。最近批准的疗法以固定的四个周期进行尽管有一个独特的机会，可以执行基于SPECT成像的病变/器官剂量测定法每个周期以计划下一个周期。该系统可以适用于其他放射线和靶向的疗法可以从基于SPECT/CT成像的计划中受益的药物，例如使用177LU PSMA的放射性疗法用于前列腺癌和Alpha发射蛋白的新兴疗法。提议的系统集成了团队和新工具过去开发的工具，为最终用户带来新的能力，以有效地计划TRT，所有数据处理都方便地在一个平台内执行。这将有很大的积极影响，因为个性化的剂量学指导方法可能会大大提高效率，而与当前任意的“一剂量合适”方法相比，保持低毒性。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Differences in tumor-to-normal organ SUV ratios measured with 68 Ga-DOTATATE PET compared with 177 Lu-DOTATATE SPECT in patients with neuroendocrine tumors.

DOI：
10.1097/mnm.0000000000001592
发表时间：
2022-08-01
期刊：
NUCLEAR MEDICINE COMMUNICATIONS
影响因子：
1.5
作者：
Wong, Ka Kit;Frey, Kirk A.;Niedbala, Jeremy;Kaza, Ravi K.;Worden, Francis P.;Fitzpatrick, Kellen J.;Dewaraja, Yuni K.
通讯作者：
Dewaraja, Yuni K.

Experimental validation of Monte Carlo dosimetry for therapeutic beta emitters with radiochromic film in a 3D-printed phantom.

DOI：
10.1002/mp.15926
发表时间：
2023-01
期刊：
MEDICAL PHYSICS
影响因子：
3.8
作者：
Van, Benjamin;Dewaraja, Yuni K.;Niedbala, Jeremy T.;Rosebush, Gerrid;Kazmierski, Matthew;Hubers, David;Mikell, Justin K.;Wilderman, Scott J.
通讯作者：
Wilderman, Scott J.

Technical note: Impact of dose voxel kernel (DVK) values on dosimetry estimates in 177 Lu and 90 Y radiopharmaceutical therapy (RPT) applications.

技术说明：剂量体素核 (DVK) 值对 177 Lu 和 90 Y 放射性药物治疗 (RPT) 应用中剂量测定估计的影响。

DOI：
10.1002/mp.16729
发表时间：
2024
期刊：
Medical physics
影响因子：
3.8
作者：
Danieli,Rachele;Pistone,Daniele;Tranel,Jonathan;Botta,Francesca;Uribe-Munoz,Carlos;Raspanti,Davide;Salvat,Francesc;Wilderman,ScottJ;Bardiès,Manuel;Amato,Ernesto;Dewaraja,YuniK;Cremonesi,Marta
通讯作者：
Cremonesi,Marta

Accuracy and uncertainty analysis of reduced time point imaging effect on time-integrated activity for 177Lu-DOTATATE PRRT in clinical patients and realistic simulations.

减少时间点成像对临床患者 177Lu-DOTATATE PRRT 时间积分活动的影响的准确性和不确定性分析以及真实模拟。