Abstract：
Peptide receptor radionuclide therapy presents the possibility of tracing and quantifying the uptake of the drug in the body and performing dosimetry, potentially allowing individualization of treatment schemes. However, the details of how neuroendocrine tumors (NETs) respond to different absorbed doses are insufficiently known. Here, we investigated the relationship between tumor-absorbed dose and tumor response in a cohort of patients with NETs treated with [177Lu]Lu-DOTATATE. Methods: This was a retrospective study based on 69 tumors in 32 patients treated within a clinical trial. Dosimetry was performed at each cycle of [177Lu]Lu-DOTATATE, rendering 366 individual absorbed dose assessments. Hybrid planar-SPECT/CT imaging using [177Lu]Lu-DOTATATE was used, including quantitative SPECT reconstruction, voxel-based absorbed dose rate calculation, semiautomatic image segmentation, and partial-volume correction. Changes in tumor volume were used to determine tumor response. The volume for each tumor was manually delineated on consecutive CT scans, giving a total of 712 individual tumor volume assessments. Tumors were stratified according to grade. The relationship between absorbed dose and response was investigated using mixed-effects models and logistic regression. Tumors smaller than 4 cm3 were excluded. Results: In grade 2 NETs, a clear relationship between absorbed dose and volume reduction was observed. Our observations suggest a 90% probability of partial tumor response for an accumulated tumor-absorbed dose of at least 135 Gy. Conclusion: Our findings are in accordance with previous observations regarding the relationship between tumor shrinkage and absorbed dose. Moreover, our data suggest an absorbed dose threshold for partial response in grade 2 NETs. These observations provide valuable insights for the design of dosimetry-guided peptide receptor radionuclide therapy schemes.
摘要：
肽受体放射性核素治疗提供了追踪和定量体内药物摄取并进行剂量测定的可能性，可能允许个性化的治疗方案。然而,神经内分泌肿瘤(NETs)对不同吸收剂量的反应细节尚不清楚.这里,我们在接受[177Lu]Lu-DOTATATE治疗的NETs患者队列中调查了肿瘤吸收剂量与肿瘤反应之间的关系.方法：这是一项回顾性研究，基于在临床试验中接受治疗的32例患者中的69例肿瘤。在[177Lu]Lu-DOTATATE的每个周期进行剂量测定，提供366个个体吸收剂量评估。使用[177Lu]Lu-DOTATATE进行混合平面-SPECT/CT成像，包括定量SPECT重建，基于体素的吸收剂量率计算，半自动图像分割，和部分音量校正。肿瘤体积的变化用于确定肿瘤反应。在连续的CT扫描中手动描绘每个肿瘤的体积，给出总共712个个体肿瘤体积评估。根据分级对肿瘤进行分层。使用混合效应模型和逻辑回归研究了吸收剂量与反应之间的关系。排除小于4cm3的肿瘤。结果：在2级NET中，观察到吸收剂量与体积减少之间存在明确的关系.我们的观察结果表明，对于至少135Gy的累积肿瘤吸收剂量，部分肿瘤反应的可能性为90％。结论：我们的发现与先前关于肿瘤缩小与吸收剂量之间关系的观察结果一致。此外，我们的数据提示2级NETs部分缓解的吸收剂量阈值.这些观察结果为剂量学指导的肽受体放射性核素治疗方案的设计提供了有价值的见解。
