Dose-Response in Radionuclide Therapy

放射性核素治疗的剂量反应

• 批准号: 7413613
• 负责人: George Sgouros
• 金额: $ 39.08万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7413613
• 关键词: 3-Dimensional; Accounting; Address; Anatomic Models; Anatomy; Classification; Clinical; Collection; Complex; Computer software; Data; Data Analyses; Data Collection; Discipline of Nuclear Medicine; Doctor of Philosophy; Dose; Dose-Rate; Evaluation; FLT3 ligand; Hematopoietic; Ibritumomab Tiuxetan; Image; Malignant neoplasm of thyroid; Methodology; Modality; Modeling; Non-Hodgkin' s Lymphoma; Organ; Patients; Prior Therapy; Probability; Radioisotopes; Radionuclide therapy; Rate; Role; Spatial Distribution; Standards of Weights and Measures; Therapeutic; Three-Dimensional Imaging; Thyroid Diseases; Thyroid carcinoma; Toxic effect; United States National Institutes of Health; Variant; Y 90 Ibritumomab Tiuxetan; base; cancer therapy; design; dosimetry; experience; improved; iodine-131-tositumomab; response; tositumomab; tumor

Targeted radionuclide therapy is being actively investigated as a potential cancer therapy modality. The relationship between absorbed dose and tumor response or normal organ toxicity is important in optimizing radionuclide therapy. Current understanding of this relationship is almost completely derived from external beam rather than radionuclide therapy experience. Using data derived from clinical radionuclide therapy studies we propose to evaluate the potential role of radionuclide dosimetry in trial design and tumor response or toxicity prediction. The following questions will be addressed by this proposal: 1. What is the relationship between estimated absorbed dose and tumor and normal organ response? 2. Does patient specific, 3-D imaging-based dosimetry provide an advantage over a simpler, standard phantom-based approach? 3. Does radiobiologic modeling that accounts for differences in absorbed dose rate and uniformity improve response prediction? 4. How does prior therapy influence hematologic toxicity and the dose-response relationship? Using 3D-ID, a patient-specific 3-D dosimetry package developed by the PI with previous NIH support, the following aims are proposed to address these questions 1.Incorporate radiobiologic modeling in 3D-ID to utilize and interpret dose-rate and spatial uniformity information in evaluating response probability. 2.1.Obtain dose-response relationships in thyroid disease patients treated with 1-131. 2.2. Obtain dose-response relationships for non-hodgkins lymphoma patients treated with non- myeloablative Tositumomab (Bexxar; 131l-anti-CD20) and Ibritumomab Tiuxetan (Zevalin; 90Y-anti-CD20). 3. Compare dose-responserelationships obtained by accounting for dose-rate, non-uniformity and patient- specific anatomy (i.e., using 3D-ID) with those obtained using a simpler, standard-phantom based methodology (OLINDA); in the NHL studies, evaluate the role of FL.T3 ligand in improving thedose-response relationship for hematologic toxicity. Dosimetry has been assumed to be the best predictor of response following radionuclide treatment. Standardized, rigorous dosimetric analyses of radionuclide therapy data are needed to evaluate this assumption, identify the level of complexity required and to understand how other factors can impact the absorbed dose vs response relationship.

靶向放射性核素治疗正在积极研究为潜在的癌症治疗方式。这 吸收剂量与肿瘤反应或正常器官毒性之间的关系对于优化很重要 放射性核素治疗。当前对这种关系的理解几乎完全来自外部 梁而不是放射性核素治疗经验。使用临床放射性核素治疗的数据 我们建议评估放射性核素剂量测定在试验设计和肿瘤中的潜在作用 反应或毒性预测。该提议将解决以下问题：1。 估计吸收剂量与肿瘤和正常器官反应之间的关系？ 2。耐心 特定的基于3-D成像的剂量法可以优于更简单的标准幻影 方法？ 3。是放射性生物学建模是否解释了吸收剂量率的差异和 均匀性改善了响应预测？ 4。先前的治疗如何影响血液学毒性和 剂量反应关系？使用3D-ID，由PI开发的患者特异性3-D剂量测定套件 在先前的NIH支持下，提出了以下目标来解决这些问题1. 3D-ID中的放射生物学建模，以利用和解释剂量率和空间均匀性信息 评估响应概率。 2.1.甲状腺疾病患者的剂量反应关系 1-131。 2.2。获得非霍奇金斯淋巴瘤患者的剂量反应关系 骨髓性tositumomab（Bexxar; 131L-Anti-CD20）和Ibritumomab Tiuxetan（Zevalin; 90Y-ANTI-CD20）。 3。比较通过考虑剂量率，不均匀性和患者的剂量反应相关性 特定的解剖结构（即使用3D-ID），使用更简单的标准基于基于标准的解剖结构 方法论（Olinda）；在NHL研究中，评估fl.t3配体在改善thedose响应中的作用 血液学毒性的关系。剂量法被认为是反应的最佳预测指标 放射性核素处理后。标准化的，严格的放射性核素治疗数据的分析 需要评估这一假设，确定所需的复杂程度，并了解如何 其他因素可能会影响吸收的剂量与反应关系。