个体化[177Lu]Lu-PSMA-617放射配体治疗的剂量学评估在转移性去势抵抗性前列腺癌中的应用
Personalized dosimetry assessment of [177Lu]Lu-PSMA-617 radioligand therapy in the management of metastatic castration-resistant prostate cancer
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影响因子:2.4
分区:医学4区 / 核科学技术3区 生物学4区 核医学4区
发表日期:2024
作者:
Mahmood Kazemi-Jahromi, Elmira Yazdani, Najme Karamzade-Ziarati, Mahboobeh Asadi, Mahdi Sadeghi, Parham Geramifar
DOI:
10.1080/09553002.2024.2404448
摘要
前列腺特异性膜抗原（PSMA）靶向放射配体治疗（RLT）正在革新转移性去势抵抗性前列腺癌（mCRPC）患者的治疗格局。本研究旨在为伊朗mCRPC患者建立[177Lu]Lu-PSMA-617 RLT的个体化放射剂量学。共纳入12例经活检确诊的前列腺癌患者（年龄平均68.73±5.26岁），接受平均6.62±0.36 GBq的[177Lu]Lu-PSMA-617治疗。术后采用全身平面扫描（4、48及72小时）以及单次SPECT/CT成像（约48小时）获取累积活性。设计了平衡时间效率与精确度的成像方案和剂量学方法，利用SPECT/CT图像作为源/几何输入，将其导入GATE蒙特卡罗模拟工具，计算S值。依据MIRD方案，结合剂量因子和累积活性，计算了危及器官（OAR）及肿瘤病灶的吸收剂量（AD）。研究发现，肝脏、脾脏、左右肾及肿瘤的平均AD分别为0.11±0.04 Gy/GBq、0.08±0.03 Gy/GBq、0.34±0.09 Gy/GBq、0.34±0.10 Gy/GBq及0.83±0.54 Gy/GBq。其中肿瘤的AD显著高于正常组织，显示肿瘤细胞对放射药的摄取更优。结果表明，增加[177Lu]Lu-PSMA-617的给药剂量在目前研究范围内是可行的，且对OAR的副作用风险较低。未来需进一步临床随访验证高剂量方案的安全性和疗效。
Abstract
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is revolutionizing the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) patients. This study aimed to establish patient-specific radiation dosimetry for [177Lu]Lu-PSMA-617 RLT in Iranian patients with mCRPC.Twelve biopsy-proven prostate cancer patients (aged 68.73 ± 5.26 yr) underwent 6.62 ± 0.36 GBq [177Lu]Lu-PSMA-617 RLT. Post-therapy whole-body planar scans were acquired approximately at 4, 48, and 72 h post-administration, alongside a single SPECT/CT around 48 h using Siemens Symbia T2 to obtain cumulated activity. An imaging protocol and dosimetry approach were designed to balance between time efficacy and accuracy in post-therapeutic dosimetry. Using accurate activity calibration, S-values were calculated by importing SPECT/CT images as the source/geometry into the Geant4 application for the tomographic emission (GATE) Monte Carlo (MC) toolkit. The Medical Internal Radiation Dose (MIRD) scheme was followed for subsequent absorbed dose (AD) calculations in organs at risk (OAR) and tumoral lesions using the dose actor and accumulated activities for precise dose estimations.Using the MC approach, the mean ADs to the liver, spleen, right and left kidneys, and tumor lesions were 0.11 ± 0.04 Gy/GBq, 0.08 ± 0.03 Gy/GBq, 0.34 ± 0.09 Gy/GBq, 0.34 ± 0.10 Gy/GBq, and 0.83 ± 0.54 Gy/GBq, respectively. Notably, tumoral lesions demonstrated significantly higher ADs, indicating enhanced uptake of radiopharmaceuticals by malignant cells.This study indicates that the ADs of OARs and tumoral lesions from [177Lu]Lu-PSMA-617 RLT in patients with mCRPC are consistent with existing literature. The dosimetry findings suggest that increasing the administered activity of [177Lu]Lu-PSMA-617 RLT is feasible and does not pose a significant risk of adverse effects on OARs, as supported by our data. However, to validate the safety and efficacy of higher doses, further clinical follow-up studies are recommended.