A Novel Dose Calculation Method for Targeted Radionuclide Therapy

一种新的放射性核素靶向治疗剂量计算方法

• 批准号: 8121451
• 负责人: FIRAS MOURTADA
• 金额: $ 31.64万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-05 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8121451
• 关键词: 90Y; Accounting; Address; Agreement; Anatomy; Beta Particle; Biodistribution; Biological; Biological Markers; Body Weight; Bone Marrow; Bone Pain; Brachytherapy; Cancer Patient; Cells; Clinic; Clinical; Clinical Treatment; Clinical Trials; Clinical Trials Design; Common Terminology Criteria for Adverse Events; Complex; Coupled; Data; Data Analyses; Deposition; Development; Discipline of Nuclear Medicine; Dose; Dose-Limiting; Dose-Rate; Echo-Planar Imaging; Elements; Equation; Film; Generic Drugs; Goals; Half-Life; Heterogeneity; Hour; Human; Hybrids; Image; Inferior; Investigation; Kidney; Kinetics; Left; Malignant - descriptor; Measurement; Measures; Medical; Medical Imaging; Metabolic; Methodology; Methods; Modeling; Monte Carlo Method; Neoplasm Metastasis; Normal tissue morphology; Organ; Outcome; PET/CT scan; Pain Measurement; Patients; Pharmacologic Substance; Phase; Phase II Clinical Trials; Predictive Value; Protocols documentation; Radiation; Radiation Oncology; Radiation Tolerance; Radiation therapy; Radioactivity; Radioisotopes; Radionuclide therapy; Radiopharmaceuticals; Red Marrow; Regimen; Relative (related person); Reporting; Risk; Samarium SM 153 lexidronam; Solutions; Targeted Radiotherapy; Testing; Time; Tissues; Toxic effect; Treatment Efficacy; Uncertainty; United States National Institutes of Health; University of Texas M D Anderson Cancer Center; Validation; Work; Wound Healing; base; bone; cohort; discrete data; dosimetry; experience; human tissue; imaging modality; improved; indexing; innovation; interest; internal radiation; malignant breast neoplasm; novel; public health relevance; radiation absorbed dose; repaired; response; simulation; single photon emission computed tomography; skeletal; tool; treatment planning; tumor; virtual

DESCRIPTION (provided by applicant): Targeted radiotherapy with internally administered radiopharmaceuticals has recently experienced renewed interest due to identification of better tumor biomarkers and development of new targeting agents. In any form of radiotherapy, the fraction of surviving cells, healthy organ toxicity and tumor response depend primarily on the quantity of energy deposited. The relationship between absorbed dose and malignant tissue response or normal tissue toxicity is the theme of any radiotherapy approach. The following questions will be addressed by this proposal: 1. Can we improve the accuracy of radiation absorbed dose estimate to a specific patient relative to current, simpler phantom-based methods, yet such a method be efficient enough for routine clinical use? 2) Will accounting for the temporal and spatial dose-rate gradient and tissue-response heterogeneity by using known radiobiologic models improve the predictive value of treatment efficacy and toxicity to bone marrow and kidney? Using an ultra fast discrete ordinate method (DOM) with quantitative SPECT/CT voxel-based dose engine developed by the PI with previous NIH support, the following aims are proposed to address these questions: 1) Validate the accuracy of DOM-QSPECT/CT in phantom with measurements and Monte Carlo simulations, 2) Incorporate known radiobiological effect dose (BED) models in the DOM-QSPECT/CT dose estimate and generate BED-volume-histograms for kidney, 3) Compare retrospectively DOM-QSPECT/CT dose estimates to MIRD and Monte Carlo dose estimates for a cohort of patients treated using Sm-153 EDTMP in a phase II clinical trial, and 4) Correlate the clinical outcomes (bone pain index and toxicity level to bone and kidney) to the DOM-QSPECT/CT-BED dose estimates. The proposed work is innovative because it capitalizes on a novel method to perform radiation transport in human tissue, a method that we have demonstrated to be as accurate as Monte Carlo simulations yet far more efficient for complex external beam radiotherapy regimens (i.e., computational results can be obtained within minutes compared to many hours or days for Monte Carlo). In addition, we propose the incorporation of radiobiological modeling to assess the treatment plan using the biological effective dose concept. With respect to expected outcomes, the combination of the work proposed in the four specific aims is expected to create a new platform for radiopharmaceutical dosimetry that will have a positive impact on the therapy field of nuclear medicine, in a way that will fundamentally advance the field of patient-specific internal radionuclide therapy treatment planning. PUBLIC HEALTH RELEVANCE: Targeted radiotherapy with internally administered radiopharmaceuticals has recently experienced renewed interest due to identification of better tumor biomarkers and development of new targeting agents. Our long term goal is to develop targeted radionuclide therapy planning tools comparable to those used in radiation oncology practice (e.g., for external beam and brachytherapy), in order to aid in trial design and tumor response and toxicity prediction, as well as replace the current, inferior planar image/MIRD-based dosimetry methodology. We developed a deterministic radiation transport method that we plan to validate and test in a cohort of patients from a phase II clinical trial of a skeletal targeted therapy radiopharmaceutical in Breast Cancer Patients with Bone Only Metastases.

描述（由申请人提供）：由于鉴定出更好的肿瘤生物标志物和新靶向剂的开发，用于内部施用的放射性药物的靶向放射疗法最近引起了人们的兴趣。在任何形式的放射疗法中，幸存细胞的比例，健康的器官毒性和肿瘤反应主要取决于沉积的能量量。吸收剂量与恶性组织反应或正常组织毒性之间的关系是任何放射疗法方法的主题。该提案将解决以下问题：1。相对于当前基于幻影的方法，我们是否可以提高辐射吸收剂量估计的准确性，但是这种方法足以有效地供常规临床使用？ 2）使用已知的放射性生物学模型提高治疗效率和对骨髓和肾脏的毒性的预测价值，是否会考虑时间和空间剂量率梯度和组织反应异质性？使用具有定量SPECT/CT基于Voxel的剂量引擎的超快速离散纵坐标方法（DOM），由PI开发并以前的NIH支持，提出了以下目的来解决以下问题：1）验证DOM-QSPEPT/CT的准确性在具有测量和蒙特卡洛模拟的幻影中，2）在DOM-QSPECT/CT剂量估计中纳入已知的放射生物学效应剂量（BED）模型，并为肾脏产生床量 - 固定图，3）回顾性地比较Dom-Qspect/CT剂量估计值在II期临床试验中使用SM-153 EDTMP治疗的一组患者的MIRD和MONTE CARLO剂量估计值，4）将临床结果（骨痛指数和毒性水平与骨骼和肾脏）与Dom-Qspect相关联/ CT床剂量估计。拟议的工作具有创新性，因为它利用了一种在人体组织中执行辐射运输的新方法，我们已经证明，这种方法与蒙特卡罗模拟一样准确，但对于复杂的外部束放射治疗方案而言，却更有效（即计算结果可以可以与Monte Carlo相比，可以在几分钟之内获得。此外，我们建议将放射生物学建模纳入使用生物学有效剂量概念评估治疗计划。关于预期的结果，预计在四个特定目标中提出的工作的组合将为放射性药物剂量测定创建一个新的平台，该平台将对核医学治疗领域产生积极影响，从而从根本上推进该领域特定于患者的内部放射性核素治疗计划。 公共卫生相关性：由于鉴定出更好的肿瘤生物标志物和新靶向剂的发展，对内部管理的放射药物的有针对性放疗最近引起了人们的兴趣。我们的长期目标是开发有针对性的放射性核素治疗计划工具，可与辐射肿瘤学实践（例如，对于外束和近距离放射治疗）相媲美，以帮助进行试验设计，肿瘤反应和毒性预测，并取代当前，基于下平面图像/基于MIRD的剂量测定方法。我们开发了一种确定性的辐射传输方法，该方法计划在骨骼靶向治疗的II期临床试验中验证和检验的一组患者，用于仅骨转移的乳腺癌患者。