Department of Nuclear Medicine, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Pattern Recognition Lab, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Ann Nucl Med. 2020 Apr;34(4):244-253. doi: 10.1007/s12149-020-01440-3. Epub 2020 Feb 29.
Patients with advanced neuroendocrine tumors (NETs) of the midgut are suitable candidates for Lu-DOTATOC therapy. Integrated SPECT/CT systems have the potential to help improve the accuracy of patient-specific tumor dosimetry. Dose estimations to target organs are generally performed using the Medical Internal Radiation Dose scheme. We present a novel Monte Carlo-based voxel-wise dosimetry approach to determine organ- and tumor-specific total tumor doses (TTD).
A cohort of 14 patients with histologically confirmed metastasized NETs of the midgut (11 men, 3 women, 62.3 ± 11.0 years of age) underwent a total of 39 cycles of Lu-DOTATOC therapy (mean 2.8 cycles, SD ± 1 cycle). After the first cycle of therapy, regions of interest were defined manually on the SPECT/CT images for the kidneys, the spleen, and all 198 tracer-positive tumor lesions in the field of view. Four SPECT images, taken at 4 h, 24 h, 48 h and 72 h after injection of the radiopharmaceutical, were used to determine their effective half-lives in the structures of interest. The absorbed doses were calculated by a three-dimensional dosimetry method based on Monte Carlo simulations. TTD was calculated as the sum of all products of single tumor doses with single tumor volumes divided by the sum of all tumor volumes.
The average dose values per cycle were 3.41 ± 1.28 Gy (1.91-6.22 Gy) for the kidneys, 4.40 ± 2.90 Gy (1.14-11.22 Gy) for the spleen, and 9.70 ± 8.96 Gy (1.47-39.49 Gy) for all Lu-DOTATOC-positive tumor lesions. Low- and intermediate-grade tumors (G 1-2) absorbed a higher TTD compared to high-grade tumors (G 3) (signed-rank test, p = < 0.05). The pre-therapeutic chromogranin A (CgA) value and the TTD correlated significantly (Pearson correlation: = 0.67, p = 0.01). Higher TTD resulted in a significant decrease of CgA after therapy.
These results suggest that Monte Carlo-based voxel-wise dosimetry is a very promising tool for predicting the absorbed TTD based on histological and clinical parameters.
患有中肠神经内分泌肿瘤（NET）的晚期患者是 Lu-DOTATOC 治疗的合适人选。集成 SPECT/CT 系统有可能帮助提高患者特定肿瘤剂量测定的准确性。通常使用医学内部辐射剂量方案对靶器官进行剂量估计。我们提出了一种新的基于蒙特卡罗的体素剂量测定方法，用于确定器官和肿瘤特异性总肿瘤剂量（TTD）。
一组 14 名经组织学证实患有中肠转移性 NET 的患者（11 名男性，3 名女性，62.3±11.0 岁）接受了总共 39 个周期的 Lu-DOTATOC 治疗（平均 2.8 个周期，标准差±1 个周期）。在治疗的第一个周期后，手动在 SPECT/CT 图像上为肾脏、脾脏和视野中所有 198 个示踪阳性肿瘤病变定义了感兴趣区域。使用四个 SPECT 图像，在注射放射性药物后 4、24、48 和 72 小时采集，以确定它们在感兴趣结构中的有效半衰期。通过基于蒙特卡罗模拟的三维剂量测定方法计算吸收剂量。TTD 计算为所有肿瘤剂量与单个肿瘤体积的乘积之和除以所有肿瘤体积之和。
每个周期的平均剂量值分别为肾脏 3.41±1.28Gy（1.91-6.22Gy）、脾脏 4.40±2.90Gy（1.14-11.22Gy）和所有 Lu-DOTATOC 阳性肿瘤病变 9.70±8.96Gy（1.47-39.49Gy）。低级别和中级肿瘤（G1-2）吸收的 TTD 高于高级别肿瘤（G3）（符号秩检验，p<0.05）。治疗前嗜铬粒蛋白 A（CgA）值与 TTD 显著相关（Pearson 相关系数：=0.67，p=0.01）。较高的 TTD 导致治疗后 CgA 显著下降。
这些结果表明，基于蒙特卡罗的体素剂量测定是一种非常有前途的工具，可以根据组织学和临床参数预测吸收的 TTD。
