个性化剂量测定评估[177Lu]Lu-PSMA-617放射性配体疗法在转移性耐受性前列腺癌治疗中的应用。

Mahmood Kazemi-Jahromi, Elmira Yazdani, Najme Karamzade-Ziarati, Mahboobeh Asadi, Mahdi Sadeghi, Parham Geramifar
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引用次数: 0

摘要

简介:前列腺特异性膜抗原(PSMA)靶向放射性配体疗法(RLT)正在彻底改变转移性耐阉割前列腺癌(mCRPC)患者的治疗现状。本研究旨在为伊朗mCRPC患者建立[177Lu]Lu-PSMA-617 RLT的患者特异性辐射剂量学:方法:12 名经活检证实的前列腺癌患者(年龄为 68.73 ± 5.26 岁)接受了 6.62 ± 0.36 GBq [177Lu]Lu-PSMA-617 RLT。大约在用药后4、48和72小时进行了治疗后全身平面扫描,并在48小时左右使用西门子Symbia T2进行了一次SPECT/CT扫描,以获得累积活性。成像方案和剂量测定方法的设计兼顾了时间效力和治疗后剂量测定的准确性。利用精确的放射性活度校准,将 SPECT/CT 图像作为源/几何图形导入用于断层发射的 Geant4 应用程序(GATE)蒙特卡罗(MC)工具包,从而计算出 S 值。在随后的吸收剂量(AD)计算中,采用了医用内部辐射剂量(MIRD)方案,利用剂量行为体和累积活度对高危器官(OAR)和肿瘤病灶进行精确剂量估算:采用 MC 方法,肝脏、脾脏、左右肾脏和肿瘤病灶的平均吸收剂量分别为 0.11 ± 0.04 Gy/GBq、0.08 ± 0.03 Gy/GBq、0.34 ± 0.09 Gy/GBq、0.34 ± 0.10 Gy/GBq 和 0.83 ± 0.54 Gy/GBq。值得注意的是,肿瘤病变的 ADs 明显更高,表明恶性细胞对放射性药物的摄取增强:本研究表明,在mCRPC患者中,[177Lu]Lu-PSMA-617 RLT对OAR和肿瘤病变的AD与现有文献一致。剂量测定结果表明,增加[177Lu]Lu-PSMA-617 RLT的给药活性是可行的,而且不会对OARs造成显著的不良影响风险,我们的数据也证明了这一点。不过,为了验证更大剂量的安全性和有效性,建议进一步开展临床跟踪研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Personalized dosimetry assessment of [177Lu]Lu-PSMA-617 radioligand therapy in the management of metastatic castration-resistant prostate cancer.

Introduction: 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.

Method: 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.

Results: 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.

Conclusions: 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.

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