Dose-Response in Radionuclide Therapy

靶向放射性核素治疗作为一种潜在的癌症治疗方式正在积极研究。的 吸收剂量与肿瘤反应或正常器官毒性之间的关系在优化中是重要的。 放射性核素治疗目前对这种关系的理解几乎完全来自外部 而不是放射性核素治疗经验。使用来自临床放射性核素治疗的数据 我们建议开展的研究旨在评估放射性核素剂量测定在试验设计和肿瘤治疗中的潜在作用。 反应或毒性预测。本提案将解决以下问题：1.是什么 估计吸收剂量与肿瘤和正常器官反应的关系？2.患者是否 特定基于3-D成像的剂量测定提供了优于更简单的基于标准体模的剂量测定的优点 接近？3.放射生物学建模是否能解释吸收剂量率和 均匀性改善响应预测？4.既往治疗如何影响血液学毒性， 剂量反应关系？使用3D-ID，PI开发的患者特定3-D剂量测定包 在美国国立卫生研究院以前的支持下，提出了以下目标来解决这些问题：1.纳入 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.获得接受治疗的甲状腺疾病患者的剂量-反应关系 1 - 131 2.2.获得非霍奇金淋巴瘤患者接受非- 清髓性托西莫单抗（Bexxar; 131 l-抗-CD20）和替伊莫单抗（Zevalin; 90 Y-抗-CD20）。 3.比较通过考虑剂量率、非均匀性和患者- 特定解剖结构（即，使用3D-ID）与使用更简单的基于标准体模获得的那些 方法学（OLINDA）;在NHL研究中，评价FL.T3配体在改善剂量反应中的作用 血液学毒性的关系。剂量测定被认为是反应的最佳预测因子 放射性核素治疗后。放射性核素治疗数据的标准化、严格的剂量测定分析 需要评估这一假设，确定所需的复杂程度，并了解如何 其他因素也会影响吸收剂量与响应关系。

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.