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: 7888739
• 负责人: FIRAS MOURTADA
• 金额: $ 32.62万
• 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 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7888739
• 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）：由于更好的肿瘤生物标志物的鉴定和新靶向剂的开发，体内施用放射性药物的靶向放射治疗最近重新引起人们的兴趣。在任何形式的放射治疗中，存活细胞的比例、健康器官的毒性和肿瘤反应主要取决于所沉积的能量的量。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治疗方法的主题。该提案将解决以下问题： 1. 相对于当前更简单的基于模型的方法，我们能否提高特定患者的辐射吸收剂量估计的准确性，但这种方法对于常规临床使用足够有效？ 2）使用已知的放射生物学模型来解释时空剂量率梯度和组织反应异质性是否会提高治疗效果和对骨髓和肾脏的毒性的预测价值？使用由 PI 在先前 NIH 支持下开发的超快速离散坐标方法 (DOM) 以及基于定量 SPECT/CT 体素的剂量引擎，提出以下目标来解决这些问题： 1) 验证 DOM-QSPECT/CT 的准确性在模型中进行测量和蒙特卡罗模拟，2) 将已知的放射生物效应剂量 (BED) 模型纳入 DOM-QSPECT/CT 剂量估计并生成 BED 体积直方图对于肾脏，3) 将 DOM-QSPECT/CT 剂量估计值与 MIRD 和 Monte Carlo 剂量估计值进行回顾性比较，对在 II 期临床试验中使用 Sm-153 EDTMP 治疗的一组患者进行比较，以及 4) 将临床结果（骨痛指数）关联起来以及对骨骼和肾脏的毒性水平）到 DOM-QSPECT/CT-BED 剂量估计。所提出的工作具有创新性，因为它利用了一种在人体组织中进行辐射传输的新方法，我们已经证明这种方法与蒙特卡罗模拟一样准确，但对于复杂的外束放射治疗方案要高效得多（即，计算结果可以与蒙特卡洛需要花费数小时或数天的时间相比，只需几分钟即可获得）。此外，我们建议结合放射生物学模型，使用生物有效剂量概念来评估治疗计划。就预期成果而言，四个具体目标中提出的工作的结合预计将创建一个新的放射性药物剂量测定平台，这将对核医学治疗领域产生积极影响，从而从根本上推动该领​​域的发展患者特定的内部放射性核素治疗治疗计划。 公共健康相关性：由于更好的肿瘤生物标志物的鉴定和新靶向药物的开发，体内放射性药物的靶向放射治疗最近重新引起了人们的兴趣。我们的长期目标是开发与放射肿瘤学实践中使用的工具（例如，用于外照射和近距离放射治疗）相当的靶向放射性核素治疗规划工具，以帮助试验设计和肿瘤反应和毒性预测，并取代当前的，基于劣质平面图像/MIRD 的剂量测定方法。我们开发了一种确定性辐射传输方法，计划在仅骨转移乳腺癌患者的骨骼靶向治疗放射性药物 II 期临床试验的一组患者中进行验证和测试。