Novel theranostic approaches using radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) have emerged for treating metastatic castration-resistant prostate cancer. The physical properties and commercial availability of ¹⁷⁷Lu make it one of the most used radionuclides for radiopharmaceutical therapy (RPT). In this literature review, we aimed at comparing the dosimetry of the most used [¹⁷⁷Lu]Lu-PSMA RPT compounds. Methods: This was a systematic review and metaanalysis of [¹⁷⁷Lu]Lu-PSMA RPT (617, I&T, and J591) dosimetry in patients with prostate cancer. Absorbed doses in Gy/GBq for each organ at risk (kidney, parotid and submandibular glands, bone marrow, liver, and lacrimal glands) and for tumor lesions (bone and nonbone lesions) were extracted from included articles. These were used to estimate the pooled average absorbed dose of each agent in Gy/GBq and in Gy/cycle, normalized to the injected activity (per cycle) used in the VISION (7.4 GBq), SPLASH (6.8 GBq), and PROSTACT trials (5.8 GBq). Results: Twenty-nine published articles comprising 535 patients were included in the metaanalysis. The pooled doses (weighted average across studies) of [¹⁷⁷Lu]Lu-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-I&T were 4.04 Gy/GBq (17 studies, 297 patients) and 4.70 Gy/GBq (10 studies, 153 patients) for the kidney (P = 0.10), 5.85 Gy/GBq (14 studies, 216 patients) and 2.62 Gy/GBq (5 studies, 86 patients) for the parotids (P < 0.01), 5.15 Gy/GBq (5 studies, 81 patients) and 4.35 Gy/GBq (1 study, 18 patients) for the submandibular glands (P = 0.56), 11.03 Gy/GBq (6 studies, 121 patients) and 19.23 Gy/GBq (3 studies, 53 patients) for the lacrimal glands (P = 0.20), 0.24 Gy/GBq (12 studies, 183 patients) and 0.19 Gy/GBq (4 studies, 68 patients) for the bone marrow (P = 0.31), and 1.11 Gy/GBq (9 studies, 154 patients) and 0.56 Gy/GBq (4 studies, 56 patients) for the liver (P = 0.05), respectively. Average tumor doses tended to be higher for [¹⁷⁷Lu]Lu-PSMA-617 than for [¹⁷⁷Lu]Lu-PSMA-I&T in soft tissue tumor lesions (4.19 vs. 2.94 Gy/GBq; P = 0.26). Dosimetry data of [¹⁷⁷Lu]Lu-J591 were limited to one published study of 35 patients with reported absorbed doses of 1.41, 0.32, and 2.10 Gy/GBq to the kidney, bone marrow, and liver, respectively. Conclusion: In this metaanalysis, there was no significant difference in absorbed dose between [¹⁷⁷Lu]Lu-PSMA-I&T and [¹⁷⁷Lu]Lu-PSMA-617. There was a possible trend toward a higher kidney dose with [¹⁷⁷Lu]Lu-PSMA-I&T and a higher tumor lesion dose with [¹⁷⁷Lu]Lu-PSMA-617. It remains unknown whether this finding has any clinical impact. The dosimetry methodologies were strikingly heterogeneous among studies, emphasizing the need for standardization.

使用针对前列腺特异性膜抗原（PSMA）的放射性药物的新型治疗诊断方法已经出现，用于治疗转移性去势抵抗性前列腺癌。 ¹⁷⁷ Lu 的物理特性和商业可用性使其成为放射性药物治疗 (RPT) 中最常用的放射性核素之一。在这篇文献综述中，我们旨在比较最常用的[ ¹⁷⁷ Lu]Lu-PSMA RPT 化合物的剂量测定。方法：这是对前列腺癌患者的[ ¹⁷⁷ Lu]Lu-PSMA RPT（617、I&T 和 J591）剂量测定的系统回顾和荟萃分析。从纳入的文章中提取每个危险器官（肾、腮腺和下颌下腺、骨髓、肝脏和泪腺）和肿瘤病变（骨和非骨病变）的吸收剂量（以 Gy/GBq 为单位）。这些用于估计每种药物的合并平均吸收剂量（以 Gy/GBq 和 Gy/周期为单位），标准化为 VISION (7.4 GBq)、SPLASH (6.8 GBq) 和 PROSTACT 试验中使用的注射活性（每个周期） （5.8 GBq）。结果：荟萃分析中纳入了 29 篇发表的文章，涉及 535 名患者。 [ ¹⁷⁷ Lu]Lu-PSMA-617 和 [ ¹⁷⁷ Lu]Lu-PSMA-I&T 的合并剂量（各研究的加权平均值）分别为 4.04 Gy/GBq（17 项研究，297 名患者）和 4.70 Gy/GBq（10 项研究， 153 名患者）肾脏（ P = 0.10），5.85 Gy/GBq（14 项研究，216 名患者）和 2.62 Gy/GBq（5 项研究，86 名患者）腮腺（ P < 0.01），5.15 Gy/GBq（5研究，81 名患者）和 4.35 Gy/GBq（1 项研究，18 名患者）下颌下腺（ P = 0.56），11.03 Gy/GBq（6 项研究，121 名患者）和 19.03 Gy/GBq（6 项研究，121 名患者）。泪腺 23 Gy/GBq（3 项研究，53 名患者）（ P = 0.20），骨髓 0.24 Gy/GBq（12 项研究，183 名患者）和 0.19 Gy/GBq（4 项研究，68 名患者）（ P = 0.20） = 0.31），肝脏分别为 1.11 Gy/GBq（9 项研究，154 名患者）和 0.56 Gy/GBq（4 项研究，56 名患者）（ P = 0.05）。在软组织肿瘤病变中，[ ¹⁷⁷ Lu]Lu-PSMA-617 的平均肿瘤剂量往往高于 [ ¹⁷⁷ Lu]Lu-PSMA-I&T（4.19 vs. 2.94 Gy/GBq； P = 0.26）。 [ ¹⁷⁷ Lu]Lu-J591 的剂量测定数据仅限于一项已发表的研究，该研究涉及 35 名患者，报告的肾脏、骨髓和肝脏吸收剂量分别为 1.41、0.32 和 2.10 Gy/GBq。结论：在本荟萃分析中，[ ¹⁷⁷ Lu]Lu-PSMA-I&T 和[ ¹⁷⁷ Lu]Lu-PSMA-617 之间的吸收剂量没有显着差异。 [ ¹⁷⁷ Lu]Lu-PSMA-I&T 可能存在更高肾脏剂量的趋势，而 [ ¹⁷⁷ Lu]Lu-PSMA-617 可能存在更高肿瘤病变剂量的趋势。目前尚不清楚这一发现是否具有任何临床影响。研究之间的剂量测定方法存在惊人的异质性，强调标准化的必要性。