Prostate-Specific Membrane Antigen Radioligand Therapy Using 177Lu-PSMA I&T and 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: Comparison of Safety, Biodistribution, and Dosimetry
Prostate-Specific Membrane Antigen Radioligand Therapy Using 177Lu-PSMA I&T and 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: Comparison of Safety, Biodistribution, and Dosimetry
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DOI：
10.2967/jnumed.121.262713
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发表时间：
2022-08-01
影响因子：
9.3
通讯作者：
Baum, Richard P.
中科院分区：
文献类型：
--
作者：
Schuchardt, Christiane;Zhang, Jingjing;Baum, Richard P.
本研究的目的是确定Lu-177标记的前列腺特异性膜抗原（PSMA）小分子Lu-177-PSMA I&T和Lu-177-PSMA-617在接受PSMA放射性配体治疗（PRLT）的转移性去势抵抗性前列腺癌（mCRPC）患者的大队列中的安全性、动力学和剂量测定。总共有138例经Ga-68-PSMA-11 PET/CT证实为进行性mCRPC和PSMA表达的患者（平均年龄70 ± 9岁;年龄范围46-90岁）接受了PRLT。51名患者接受了6.1 +/- 1.0 GBq（范围：3.4-7.6 GBq）的Lu-177-PSMA I&T，87名患者接受了6.5 +/- 1.1 GBq（范围：3.5-9.0 GBq）的Lu-177-PSMA-617。使用相同的方案对所有患者进行剂量测定。使用OLINDA软件（MIRD方案）估计平均吸收剂量。结果：Lu-177-PSMA I&T的全身半衰期（35 h）比Lu-177-PSMA-617（42 h）短。Lu-177-PSMA-617的平均全身剂量高于Lu-177-PSMA I&T（0.04 vs. 0.03戈伊/GBq，P < 0.00001）。尽管Lu-177-PSMA-617的半衰期较长，但Lu-177-PSMA-617的肾剂量低于Lu-177-PSMA I&T（0.77对0.92戈伊/GBq，P = 0.0015）。两种PSMA小分子均表现出与腮腺相当的剂量（0.5戈伊/GBq，P = 0.27）。在所有正常器官中，对于Lu-177-PSMA-617和Lu-177-PSMA I&T，泪腺表现出最高的平均吸收剂量，分别为5.1和3.7戈伊/GBq。当使用177 Lu-PSMA I&T时，所有肿瘤转移表现出比使用Lu-177-PSMA-617时更高的初始摄取，以及更短的肿瘤半衰期（P < 0.00001）。Lu-177-PSMA I&T和Lu-177-PSMA-617的平均吸收肿瘤剂量相当（5.8对5.9戈伊/GBq，P = 0.96）。所有患者均耐受治疗，无任何急性不良反应。在Lu-177-PSMA-617和Lu-177-PSMA I&T后，血红蛋白、白细胞计数和血小板计数有小的统计学显著性降低，不需要任何临床干预。结论：Lu-177-PSMA I & T和Lu-177-PSMA-617 PRLT治疗mCRPC患者均具有良好的安全性。在健康器官中，泪腺和腮腺的吸收剂量最高，但未导致任何显著的临床后遗症。与Lu-177-PSMA I&T相比，Lu-177-PSMA-617表现出更高的全身和泪腺吸收剂量，但更低的肾剂量。Lu-177-PSMA I&T和Lu-177-PSMA-617的平均吸收肿瘤剂量相当。剂量测定参数存在较大的患者间变异性。因此，基于个体患者的剂量调整似乎有利于个性化PRLT。
The objective of this study was to determine the safety, kinetics, and dosimetry of the Lu-177-labeled prostate-specific membrane antigen (PSMA) small molecules Lu-177-PSMA I&T and Lu-177-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PRLT).Methods: In total, 138 patients (mean age, 70 +/- 9 y; age range, 46-90 y) with progressive mCRPC and PSMA expression verified by Ga-68-PSMA-11 PET/CT underwent PRLT. Fifty-one patients received 6.1 +/- 1.0 GBq (range, 3.4-7.6 GBq) of Lu-177-PSMA I&T, and 87 patients received 6.5 +/- 1.1 GBq (range, 3.5-9.0 GBq) of Lu-177-PSMA-617. Dosimetry was performed on all patients using an identical protocol. The mean absorbed doses were estimated with OLINDA software (MIRD Scheme). Treatment-related adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 5.0, of the National Cancer Institute.Results: The whole-body half-lives were shorter for Lu-177-PSMA I&T (35 h) than for Lu-177-PSMA-617 (42 h). The mean whole-body dose of Lu-177-PSMA-617 was higher than that of Lu-177-PSMA I&T (0.04 vs. 0.03 Gy/GBq, P < 0.00001). Despite the longer half-life of Lu-177-PSMA-617, the renal dose was lower for Lu-177-PSMA-617 than for Lu-177-PSMA I&T (0.77 vs. 0.92 Gy/GBq, P = 0.0015). Both PSMA small molecules demonstrated a comparable dose to the parotid glands (0.5 Gy/GBq, P = 0.27). Among all normal organs, the lacrimal glands exhibited the highest mean absorbed doses, 5.1 and 3.7 Gy/GBq, for Lu-177-PSMA-617 and Lu-177-PSMA I&T, respectively. All tumor metastases exhibited a higher initial uptake when using 177Lu-PSMA I&T than when using Lu-177-PSMA-617, as well as a shorter tumor half-life (P < 0.00001). The mean absorbed tumor doses were comparable for both Lu-177-PSMA I&T and Lu-177-PSMA-617 (5.8 vs. 5.9 Gy/GBq, P = 0.96). All patients tolerated the therapy without any acute adverse effects. After Lu-177-PSMA-617 and Lu-177-PSMA I&T, there was a small, statistically significant reduction in hemoglobin, leukocyte counts, and platelet counts that did not need any clinical intervention. No nephrotoxicity was observed after either Lu-177-PSMA I&T or Lu-177-PSMA-617 PRLT.Conclusion: Both Lu-177-PSMA I&T and Lu-177-PSMA-617 PRLT dem-onstrated favorable safety in mCRPC patients. The highest absorbed doses among healthy organs were in the lacrimal and parotid glands- not, however, resulting in any significant clinical sequel. Lu-177-PSMA-617 demonstrated a higher absorbed dose to the whole-body and lacrimal glands but a lower renal dose than did Lu-177-PSMA I&T. The mean absorbed tumor doses were comparable for both Lu-177-PSMA I&T and Lu-177-PSMA-617. There was a large interpatient variability in the dosimetry parameters. Therefore, individual patient-based dosim-etry seems favorable for personalized PRLT.