用于 131I-替莫唑胺治疗非霍奇金淋巴瘤患者的患者特异性三维剂量学中纳入生物有效剂量和等效均匀剂量的方法。
Methodology to incorporate biologically effective dose and equivalent uniform dose in patient-specific 3-dimensional dosimetry for non-Hodgkin lymphoma patients targeted with 131I-tositumomab therapy.
机构信息
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109-5010, USA.
出版信息
J Nucl Med. 2010 Apr;51(4):654-9. doi: 10.2967/jnumed.109.067298. Epub 2010 Mar 17.
UNLABELLED
A 3-dimensional (3D) imaging-based patient-specific dosimetry methodology incorporating antitumor biologic effects using biologically effective dose (BED) and equivalent uniform dose (EUD) was developed in this study. The methodology was applied to the dosimetry analysis of 6 non-Hodgkin lymphoma patients with a total of 10 tumors.
METHODS
Six registered SPECT/CT scans were obtained for each patient treated with (131)I-labeled antibody. Three scans were obtained after tracer administration and 3 after therapy administration. The SPECT/CT scans were used to generate 3D images of cumulated activity. The cumulated activity images and corresponding CT scans were used as input to Monte Carlo dose-rate calculations. The dose-rate distributions were integrated over time to obtain 3D absorbed dose distributions. The time-dependent 3D cumulative dose distributions were used to generate 3D BED distributions. Techniques to incorporate the effect of unlabeled antibody (cold protein) in the BED analysis were explored. Finally, BED distributions were used to estimate an EUD for each tumor volume. Model parameters were determined from optimal fits to tumor regression data. The efficiency of dose delivery to tumors--the ratio of EUD to cumulative dose--was extracted for each tumor and correlated with patient response parameters.
RESULTS
The model developed in this study was validated for dosimetry of non-Hodgkin lymphoma patients treated with (131)I-labeled antibody. Correlations between therapy efficiency generated from the model and tumor response were observed using averaged model parameters. Model parameter determination favored a threshold for the cold effect and typical magnitude for tumor radiosensitivity parameters.
CONCLUSION
The inclusion of radiobiologic effects in the dosimetry modeling of internal emitter therapy provides a powerful platform to investigate correlations of patient outcome with planned therapy.
目的
本研究开发了一种基于三维（3D）成像的患者特异性剂量学方法，该方法结合了使用生物有效剂量（BED）和等效均匀剂量（EUD）的抗肿瘤生物效应。该方法应用于 10 个肿瘤的 6 例非霍奇金淋巴瘤患者的剂量分析。
方法
每位接受（131）I 标记抗体治疗的患者均获得 6 次注册 SPECT/CT 扫描。治疗前进行 3 次扫描，治疗后进行 3 次扫描。SPECT/CT 扫描用于生成累积活性的 3D 图像。累积活性图像和相应的 CT 扫描用作蒙特卡罗剂量率计算的输入。对剂量率分布进行时间积分，得到 3D 吸收剂量分布。使用时间依赖的 3D 累积剂量分布生成 3D BED 分布。探讨了在 BED 分析中纳入未标记抗体（冷蛋白）效应的技术。最后，使用 BED 分布估算每个肿瘤体积的 EUD。模型参数通过对肿瘤回归数据的最佳拟合来确定。从每个肿瘤中提取剂量输送效率（EUD 与累积剂量的比值），并与患者反应参数相关联。
结果
本研究开发的模型已验证用于接受（131）I 标记抗体治疗的非霍奇金淋巴瘤患者的剂量学。使用平均模型参数观察到从模型生成的治疗效率与肿瘤反应之间的相关性。模型参数的确定有利于冷效应的阈值和肿瘤放射敏感性参数的典型幅度。
结论
在内部发射体治疗的剂量建模中纳入放射生物学效应为研究患者结局与计划治疗的相关性提供了一个强大的平台。
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