¹⁷⁷Lu-PSMA-617 is an effective and novel treatment in metastatic castration-resistant prostate cancer (mCRPC). Our ability to assess response rates and therefore efficacy may be improved using predictive tools. This study investigated the predictive value of serial ¹⁷⁷Lu-PSMA-617 SPECT/CT (¹⁷⁷Lu SPECT) imaging in monitoring treatment response. Methods: Fifty-six men with progressive mCRPC previously treated with chemotherapy and novel androgen signaling inhibitor were enrolled into the LuPIN trial and received up to 6 doses of ¹⁷⁷Lu-PSMA-617 and a radiation sensitizer (3-(4-hydroxyphenyl)-2H-1-benzopyran-7-ol [NOX66]). ⁶⁸Ga-PSMA-11 and ¹⁸F-FDG PET/CT were performed at study entry and exit, and ¹⁷⁷Lu SPECT from vertex to mid thighs was performed 24 h after each treatment. SPECT quantitative analysis was undertaken at cycles 1 (baseline) and 3 (week 12) of treatment. Results: Thirty-two of the 56 men had analyzable serial ¹⁷⁷Lu SPECT imaging at both cycle 1 and cycle 3. In this subgroup, median prostate-specific antigen (PSA) progression-free survival (PFS) was 6.3 mo (95% CI, 5–10 mo) and median overall survival was 12.3 mo (95% CI, 12–24 mo). The PSA 50% response rate was 63% (20/32). ¹⁷⁷Lu SPECT total tumor volume (SPECT TTV) was reduced in 68% (22/32; median, −0.20 m³ [95% CI, −1.4 to −0.001]) and increased in 31% (10/32; median, 0.36 [95% CI, 0.1–1.4]). Any increase in SPECT TTV was associated with shorter PSA PFS (hazard ratio, 4.1 [95% CI, 1.5–11.2]; P = 0.006). An increase of 30% or more in SPECT TTV was also associated with a shorter PSA PFS (hazard ratio, 3.3 [95% CI, 1.3–8.6]; P =0.02). Tumoral SUV_max was reduced in 91% (29/32) and SUV_mean in 84% (27/32); neither was associated with PSA PFS or overall survival outcomes. PSA progression by week 12 was also associated with a shorter PSA PFS (hazard ratio, 26.5 [95% CI, 5.4–131]). In the patients with SPECT TTV progression at week 12, 50% (5/10) had no concurrent PSA progression (median PSA PFS, 4.5 mo [95% CI, 2.8–5.6 mo]), and 5 of 10 men had both PSA and SPECT TTV progression at week 12 (median PSA PFS, 2.8 mo [95% CI, 1.8–3.7 mo]). Conclusion: Increasing SPECT TTV on quantitative ¹⁷⁷Lu SPECT predicts a short PFS and may play a future role as an imaging response biomarker.

¹⁷⁷ Lu-PSMA-617 是一种有效且新颖的治疗转移性去势抵抗性前列腺癌 (mCRPC) 的方法。使用预测工具可以提高我们评估反应率和疗效的能力。^{本研究调查了连续177} Lu-PSMA-617 SPECT/CT ( ¹⁷⁷ Lu SPECT) 成像在监测治疗反应中的预测价值。方法： 56 名先前接受过化疗和新型雄激素信号抑制剂治疗的进展性 mCRPC 男性被纳入羽扇豆试验，并接受最多 6 剂 177 Lu- ^PSMA -617 和放射增敏剂（3-(4-羟苯基)- 2H-1-苯并吡喃-7-醇[NOX66]）。在研究进入和退出时进行⁶⁸ Ga-PSMA-11 和¹⁸ F-FDG PET/CT，每次治疗后 24 小时进行从头顶到大腿中部的^{177 Lu SPECT。}在治疗的第 1 周期（基线）和第 3 周期（第 12 周）进行 SPECT 定量分析。结果： 56 名男性中有 32 人在第 1 周期和第 3 周期均进行了可分析的连续 177 Lu SPECT 成像。在该亚组中，中位前列腺特异性抗原 (PSA) 无进展生存期 (PFS) 为 6.3 个月（95% ^CI，5-10 个月），中位总生存期为 12.3 个月（95% CI，12-24 个月）。PSA 50% 反应率为 63% (20/32)。¹⁷⁷ Lu SPECT 总肿瘤体积 (SPECT TTV) 减少了 68%（22/32；中位数，-0.20 m ³ [95% CI，-1.4 至 -0.001]），增加了 31%（10/32；中位数， 0.36 [95% CI，0.1–1.4]）。SPECT TTV 的任何增加都与较短的 PSA PFS 相关（风险比，4.1 [95% CI，1.5–11.2]；P = 0.006）。SPECT TTV 增加 30% 或更多也与较短的 PSA PFS 相关（风险比，3.3 [95% CI，1.3–8.6]；P = 0.02）。肿瘤 SUV_最大值降低了 91% (29/32)，SUV_平均值降低了 84% (27/32)；两者均与 PSA PFS 或总生存结果无关。第 12 周时 PSA 进展也与较短的 PSA PFS 相关（风险比，26.5 [95% CI，5.4-131]）。在第 12 周出现 SPECT TTV 进展的患者中，50% (5/10) 没有并发 PSA 进展（中位 PSA PFS，4.5 个月 [95% CI，2.8–5.6 个月]），10 名男性中有 5 人同时患有 PSA以及第 12 周时的 SPECT TTV 进展（中位 PSA PFS，2.8 个月 [95% CI，1.8–3.7 个月]）。结论：增加定量¹⁷⁷ Lu SPECT上的 SPECT TTV可以预测较短的 PFS，并且可能在未来作为成像反应生物标志物发挥作用。