[177LU] LU-PSMA-617放射性疗法的个性化剂量法评估在转移性cast割前列腺癌管理中
Personalized dosimetry assessment of [177Lu]Lu-PSMA-617 radioligand therapy in the management of metastatic castration-resistant prostate cancer
影响因子:2.40000
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
摘要
前列腺特异性膜抗原（PSMA）靶向放射性治疗（RLT）正在彻底改变转移性cast割前列腺癌（MCRPC）患者的治疗景观。 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.使用Siemens Symbia T2在48 h左右，在ADMINDITATION大约在4、48和72 h处获得了疗法后平面扫描，以获得累积活性。设计了成像方案和剂量测定方法，以在治疗后剂量法的时间效率和准确性之间取得平衡。使用准确的活性校准，通过将SPECT/CT图像作为源/几何形状导入Geant4应用程序（GATE）蒙特卡洛（MC）工具包来计算S值。遵循医学内部辐射剂量（MIRD）方案，以便使用剂量参与者和累积活动进行精确剂量估计的器官（OAR）和肿瘤病变中的随后吸收剂量（AD）计算。使用MC方法，平均AD对肝脏，Spleen，Spleen，右和左肾小管和Tumor Les les les s.1111111111114GBE/G.04 GY/g.04 gy.04 gy.04 gy/gy。 0.08±0.03 GY/GBQ，0.34±0.09 GY/GBQ，0.34±0.10 GY/GBQ和0.83±0.54 GY/GBQ。值得注意的是，肿瘤病变表现出明显更高的AD，表明通过恶性细胞对放射性药物的摄取增强。这项研究表明，MCRPC患者的OARS和[177LU] LU-PSMA-617 RLT的OAR和肿瘤病变的ADS与现有文献相稳定。剂量法的发现表明，在我们的数据支持的情况下，增加[177LU] LU-PSMA-617 RLT的施用活性是可行的，并且不会对OARS产生不利影响的重大风险。但是，为了验证更高剂量的安全性和有效性，建议进一步的临床随访研究。
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.