Vergnaud Laure, Giraudet Anne-Laure, Moreau Aurélie, Salvadori Julien, Imperiale Alessio, Baudier Thomas, Badel Jean-Noël, Sarrut David
CREATIS, CNRS UMR 5220, INSERM U 1044, Université de Lyon, INSA-Lyon, Université Lyon 1, Lyon, France.
Centre de lutte contre le cancer Léon Bérard, Lyon, France.
EJNMMI Phys. 2022 May 16;9(1):37. doi: 10.1186/s40658-022-00462-2.
The number of SPECT/CT time-points is important for accurate patient dose estimation in peptide receptor radionuclide therapy. However, it may be limited by the patient's health and logistical reasons. Here, an image-based dosimetric workflow adapted to the number of SPECT/CT acquisitions available throughout the treatment cycles was proposed, taking into account patient-specific pharmacokinetics and usable in clinic for all organs at risk.
Thirteen patients with neuroendocrine tumors were treated with four injections of 7.4 GBq of Lu-DOTATATE. Three SPECT/CT images were acquired during the first cycle (1H, 24H and 96H or 144H post-injection) and a single acquisition (24H) for following cycles. Absorbed doses were estimated for kidneys (LK and RK), liver (L), spleen (S), and three surrogates of bone marrow (L2 to L4, L1 to L5 and T9 to L5) that were compared. 3D dose rate distributions were computed with Monte Carlo simulations. Voxel dose rates were averaged at the organ level. The obtained Time Dose-Rate Curves (TDRC) were fitted with a tri-exponential model and time-integrated. This method modeled patient-specific uptake and clearance phases observed at cycle 1. Obtained fitting parameters were reused for the following cycles, scaled to the measure organ dose rate at 24H. An alternative methodology was proposed when some acquisitions were missing based on population average TDRC (named STP-Inter). Seven other patients with three SPECT/CT acquisitions at cycles 1 and 4 were included to estimate the uncertainty of the proposed methods.
Absorbed doses (in Gy) per cycle available were: 3.1 ± 1.1 (LK), 3.4 ± 1.5 (RK), 4.5 ± 2.8 (L), 4.6 ± 1.8 (S), 0.3 ± 0.2 (bone marrow). There was a significant difference between bone marrow surrogates (L2 to L4 and L1 to L5, Wilcoxon's test: p value < 0.05), and while depicting very doses, all three surrogates were significantly different than dose in background (p value < 0.01). At cycle 1, if the acquisition at 24H is missing and approximated, medians of percentages of dose difference (PDD) compared to the initial tri-exponential function were inferior to 3.3% for all organs. For cycles with one acquisition, the median errors were smaller with a late time-point. For STP-Inter, medians of PDD were inferior to 7.7% for all volumes, but it was shown to depend on the homogeneity of TDRC.
The proposed workflow allows the estimation of organ doses, including bone marrow, from a variable number of time-points acquisitions for patients treated with Lu-DOTATATE.
在肽受体放射性核素治疗中，SPECT/CT时间点的数量对于准确估算患者剂量至关重要。然而，这可能会受到患者健康状况和后勤因素的限制。在此，我们提出了一种基于图像的剂量学工作流程，该流程适应于整个治疗周期中可用的SPECT/CT采集数量，同时考虑了患者特异性药代动力学，并且可在临床上用于所有危险器官。
13例神经内分泌肿瘤患者接受了4次7.4GBq的镥-奥曲肽注射治疗。在第一个周期内采集了3张SPECT/CT图像（注射后1小时、24小时和96小时或144小时），后续周期仅采集一次（24小时）。估算了肾脏（左肾和右肾）、肝脏、脾脏以及三个骨髓替代部位（腰2至腰4、腰1至腰5和胸9至腰5）的吸收剂量，并进行了比较。通过蒙特卡罗模拟计算三维剂量率分布。在器官层面上对体素剂量率进行平均。获得的时间剂量率曲线（TDRC）采用三指数模型进行拟合并进行时间积分。该方法模拟了在第1周期观察到的患者特异性摄取和清除阶段。将获得的拟合参数用于后续周期，并按比例调整至24小时时测量的器官剂量率。当某些采集数据缺失时，基于总体平均TDRC提出了另一种方法（命名为STP-Inter）。另外纳入了7例在第1周期和第4周期有3次SPECT/CT采集的患者，以评估所提出方法的不确定性。
每个周期的吸收剂量（单位：Gy）分别为：左肾3.1±1.1、右肾3.4±1.5、肝脏4.5±2.8、脾脏4.6±1.8、骨髓0.3±0.2。骨髓替代部位之间存在显著差异（腰2至腰4和腰1至腰5，Wilcoxon检验：p值<0.05），并且在描述剂量时，所有三个替代部位与本底剂量均存在显著差异（p值<0.01）。在第1周期，如果24小时的采集数据缺失并进行近似处理，与初始三指数函数相比，所有器官的剂量差异百分比（PDD）中位数均低于3.3%。对于仅有一次采集的周期，较晚时间点的中位数误差较小。对于STP-Inter，所有体积的PDD中位数均低于7.7%，但结果显示其取决于TDRC的均匀性。
所提出的工作流程能够根据镥-奥曲肽治疗患者的不同数量时间点采集数据估算包括骨髓在内的器官剂量。
