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Abstract：
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.
摘要：
已经出现了使用靶向前列腺特异性膜抗原（PSMA）的放射性药物治疗转移性去势抵抗性前列腺癌的新型治疗方法。177Lu的物理性质和商业可用性使其成为放射性药物治疗（RPT）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[177Lu]Lu-PSMARPT化合物的剂量学。方法：这是[177Lu]Lu-PSMARPT(617，I&T，和J591）前列腺癌患者的剂量学。每个危险器官的吸收剂量（Gy/GBq，腮腺和颌下腺，骨髓,肝脏,和泪腺）和肿瘤病变（骨和非骨病变）从纳入的文章中提取。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（7.4GBq）中使用的注射活性（每个周期），SPLASH（6.8GBq），和PROSTACT试验（5.8GBq）。结果：包含535名患者的29篇发表的文章被纳入荟萃分析。[177Lu]Lu-PSMA-617和[177Lu]Lu-PSMA-I&T的合并剂量（各研究的加权平均值）为4.04Gy/GBq（17项研究，297名患者）和4.70Gy/GBq（10项研究，153名患者）用于肾脏（P=0.10），5.85Gy/GBq（14项研究，216例患者）和2.62Gy/GBq（5项研究，86例)为腮腺炎(P<0.01)，5.15Gy/GBq(5项研究，81例患者）和4.35Gy/GBq（1项研究，18例患者）下颌下腺（P=0.56），11.03Gy/GBq（6项研究，121例患者）和19.23Gy/GBq（3项研究，53例）泪腺（P=0.20），0.24Gy/GBq（12项研究，183名患者）和0.19Gy/GBq（4项研究，68例患者）对于骨髓（P=0.31），和1.11Gy/GBq(9项研究，154例患者）和0.56Gy/GBq（4项研究，56例患者）为肝脏（P=0.05），分别。在软组织肿瘤病变中，[177Lu]Lu-PSMA-617的平均肿瘤剂量往往高于[177Lu]Lu-PSMA-I＆T（4.19vs.2.94Gy/GBq；P=0.26）。[177Lu]Lu-J591的剂量学数据仅限于一项已发表的35例患者的研究，报告的肾脏吸收剂量为1.41、0.32和2.10Gy/GBq，骨髓,还有肝脏,分别。结论：在这项荟萃分析中，[177Lu]Lu-PSMA-I&T与[177Lu]Lu-PSMA-617的吸收剂量无显著差异。[177Lu]Lu-PSMA-I＆T的肾脏剂量可能更高，而[177Lu]Lu-PSMA-617的肿瘤病变剂量可能更高。目前尚不清楚这一发现是否有任何临床影响。剂量学方法在研究中具有惊人的异质性，强调标准化的必要性。
