[¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA) is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC). [¹⁷⁷Lu]Lu-PSMA SPECT/CT 24 h after injection has shown potential as a response biomarker for [¹⁷⁷Lu]Lu-PSMA therapy but is not convenient for patients. This study investigated 4-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT as an alternative to 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT for evaluation of treatment response. Methods: This prospective analysis enrolled 23 patients diagnosed with mCRPC commencing [¹⁷⁷Lu]Lu-PSMA-I&T therapy. Two patients were excluded because of incomplete imaging data. Posttherapy SPECT/CT was performed at 4 and 24 h after the first dose and 4 h after the second dose. Baseline [⁶⁸Ga]Ga-PSMA-11 PET/CT and 4- and 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT were analyzed both visually and semiquantitatively. Bland–Altman plots assessed agreement of semiquantitative parameters from the 4- and 24-h scans. Quantitative assessment of the change in the total tumor volume (TTV) on the 4-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT after the first and second doses was correlated to patient outcomes. Results: All patients had mCRPC previously treated with an androgen receptor pathway inhibitor, and 11 (52%) received prior taxane chemotherapy. Median age was 78 y, and median prostate-specific antigen level was 54 ng/mL. On visual analysis, disease distribution was unchanged among the 3 imaging methods. Eleven patients (52%) had a median of 1 lesion not identified on 4-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT compared with 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT. All missed lesions on the 4-h [¹⁷⁷Lu]Lu SPECT/CT were smaller than 2 cm. Mean differences and agreement between 4- and 24-h SPECT/CT quantitative parameters were within acceptable bounds for lesion number, SUV_max, and SUV_mean, with higher variation observed for TTV. The change in TTV between dose 1 and 2 [¹⁷⁷Lu]Lu-PSMA SPECT/CT predicted prostate-specific antigen progression-free survival. Conclusion: [¹⁷⁷Lu]Lu-PSMA SPECT/CT at 4 h after injection appears a promising alternative to 24-h [¹⁷⁷Lu]Lu-PSMA SPECT/CT for treatment response assessment, with improved patient convenience.

[¹⁷⁷Lu]Lu 前列腺特异性膜抗原 （PSMA） 是转移性去势抵抗性前列腺癌 （mCRPC） 的有效治疗方法。[¹⁷⁷Lu]注射后 24 小时 Lu-PSMA SPECT/CT 已显示出作为 [¹⁷⁷Lu]Lu-PSMA 治疗的反应生物标志物的潜力，但对患者不方便。本研究调查了 4 小时 [¹⁷⁷Lu]Lu-PSMA SPECT/CT 作为 24 小时 [¹⁷⁷Lu]Lu-PSMA SPECT/CT 的替代疗法来评估治疗反应。方法：这项前瞻性分析招募了 23 名被诊断患有 mCRPC 的患者，这些患者开始了 [¹⁷⁷Lu]Lu-PSMA-I&T 治疗。2 例患者因影像学资料不完整而被排除在外。治疗后 SPECT/CT 在第一次给药后 4 和 24 h 以及第二次给药后 4 h 进行。对基线 [⁶⁸Ga]Ga-PSMA-11 PET/CT 以及 4 小时和 24 小时 [¹⁷⁷Lu]Lu-PSMA SPECT/CT 进行目视和半定量分析。Bland-Altman 图评估了 4 小时和 24 小时扫描的半定量参数的一致性。定量评估第一剂和第二剂后 4 小时 [¹⁷⁷Lu]Lu-PSMA SPECT/CT 上总肿瘤体积 （TTV） 的变化与患者结局相关。结果：所有患者既往接受过雄激素受体通路抑制剂治疗的 mCRPC，11 例 （52%） 既往接受过紫杉烷类化疗。中位年龄为 78 岁，中位前列腺特异性抗原水平为 54 ng/mL。在视觉分析中，3 种成像方法之间的疾病分布没有变化。11 例患者 （52%） 在 4 小时 [¹⁷⁷Lu]Lu-PSMA SPECT/CT 中与 24 小时 [¹⁷⁷Lu]Lu-PSMA SPECT/CT 相比，中位有 1 个病灶未被发现。4 小时 [¹⁷⁷Lu]Lu SPECT/CT 上所有漏诊病灶均小于 2 cm。 4 小时和 24 小时 SPECT/CT 定量参数之间的平均差异和一致性在病灶数量、SUV_max 和 SUV_平均值的可接受范围内，观察到 TTV 的变化更大。剂量 1 和 2 之间 TTV 的变化 [¹⁷⁷Lu]Lu-PSMA SPECT/CT 预测了前列腺特异性抗原无进展生存期。结论： 注射后 4 h 的 [¹⁷⁷Lu]Lu-PSMA SPECT/CT 似乎是 24 h [¹⁷⁷Lu]Lu-PSMA SPECT/CT 的有前途的替代治疗反应评估，提高了患者的便利性。