¹⁷⁷Lu-PSMA is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC). Our ability to assess response rates and adjust treatment may be improved using predictive tools. This study aimed to evaluate change in ¹⁷⁷Lu-PSMA SPECT quantitative parameters to monitor treatment response. Methods: One hundred twenty-seven men with progressive mCRPC previously treated with androgen-signaling inhibition (99%) and chemotherapy (71%) received a median of 3 (interquartile range [IQR], 2–5) 8-GBq (IQR, 8–8.5 GBq) doses of ¹⁷⁷Lu-PSMA-I&T. Imaging included ⁶⁸Ga-PSMA-11 PET/CT (SUV_max > 15 at a single site and > 10 at all sites > 2 cm), diagnostic CT, and ¹⁷⁷Lu SPECT/CT from vertex to mid thigh (24 h after treatment). ¹⁷⁷Lu SPECT/CT quantitative analysis was undertaken at cycles 1 (baseline) and 2 (week 6) of treatment. Clinical and biochemical results were assessed to evaluate prostate-specific antigen (PSA) progression-free survival (PFS) and overall survival (OS). Results: A PSA reduction of more than 50% was seen in 58% (74/127). The median PSA PFS was 6.1 mo (95% CI, 5.5–6.7), and OS was 16.8 mo (95% CI, 13.5–20.1). At the time of analysis, 41% (52/127) were deceased. At baseline and week 6, 76% (96/127) had analyzable serial ¹⁷⁷Lu SPECT/CT imaging. SPECT total tumor volume (TTV) was reduced between baseline and week 6 in 74% (71/96; median, −193; IQR, −486 to −41). Any increase in SPECT TTV between baseline and week 6 was associated with significantly shorter PSA PFS (hazard ratio, 2.5; 95% CI, 1.5–4.2; P = 0.0008) but not OS. Median PSA PFS in those with an increase in SPECT TTV was 3.7 mo (95% CI, 2.8–6.8), compared with 6.7 mo (95% CI, 5.8–10.6) in those with no increase in SPECT TTV. An increase in SPECT TTV greater than 20% was also associated with PSA PFS (hazard ratio, 1.9; 95% CI, 1.2–3.0; P = 0.008) but less significantly than any change in SPECT TTV. There was a significant difference in PSA PFS between patients with both increased PSA and SPECT TTV and patients with reduced SPECT TTV and PSA (median, 2.8 vs. 9.0 mo; P < 0.0001). Conclusion: Increasing PSMA SPECT TTV on quantitative ¹⁷⁷Lu SPECT/CT predicts short progression-free survival and may play a future role as an imaging response biomarker, identifying when to cease or intensify ¹⁷⁷Lu-PSMA therapy.

¹⁷⁷ Lu-PSMA 是治疗转移性去势抵抗性前列腺癌 (mCRPC) 的有效方法。使用预测工具可以提高我们评估缓解率和调整治疗的能力。本研究旨在评估¹⁷⁷ Lu-PSMA SPECT 定量参数的变化以监测治疗反应。方法： 127 名患有进展性 mCRPC 的男性先前接受过雄激素信号抑制 (99%) 和化疗 (71%)，接受了中位数为 3（四分位距 [IQR]，2-5）的 8-GBq（IQR， 8–8.5 GBq) 剂量的¹⁷⁷ Lu-PSMA-I&T。影像学检查包括⁶⁸ Ga-PSMA-11 PET/CT（单个部位 SUV_最大值> 15，所有部位 > 2 厘米，SUV 最大值 > 10）、诊断 CT 和从头顶到大腿中部的¹⁷⁷ Lu SPECT/CT（治疗后 24 小时） ）。 ¹⁷⁷ Lu SPECT/CT 定量分析在治疗的第 1 周期（基线）和第 2 周期（第 6 周）进行。评估临床和生化结果以评估前列腺特异性抗原（PSA）无进展生存期（PFS）和总生存期（OS）。结果： 58% (74/127) 的患者 PSA 下降超过 50%。中位 PSA PFS 为 6.1 个月（95% CI，5.5–6.7），OS 为 16.8 个月（95% CI，13.5–20.1）。截至分析时，41% (52/127) 已死亡。在基线和第 6 周，76% (96/127) 进行了可分析的连续¹⁷⁷ Lu SPECT/CT 成像。 SPECT 总肿瘤体积 (TTV) 在基线和第 6 周之间减少了 74%（71/96；中位数，-193；IQR，-486 至 -41）。基线和第 6 周之间 SPECT TTV 的任何增加均与 PSA PFS 显着缩短相关（风险比，2.5；95% CI，1.5–4.2； P = 0.0008），但与 OS 无关。 SPECT TTV 增加的患者的中位 PSA PFS 为 3.7 个月（95% CI，2.8–6.8），而 SPECT TTV 未增加的患者的中位 PSA PFS 为 6.7 个月（95% CI，5.8–10.6）。 SPECT TTV 增加超过 20% 也与 PSA PFS 相关（风险比，1.9；95% CI，1.2-3.0； P = 0.008），但不如 SPECT TTV 的任何变化显着。 PSA 和 SPECT TTV 均升高的患者与 SPECT TTV 和 PSA 降低的患者之间 PSA PFS 存在显着差异（中位数为 2.8 个月与 9.0 个月； P < 0.0001）。结论：增加定量¹⁷⁷ Lu SPECT/CT 上的 PSMA SPECT TTV 可预测短期无进展生存期，并可能在未来作为成像反应生物标志物发挥作用，确定何时停止或加强¹⁷⁷ Lu-PSMA 治疗。