¹⁸F-rhPSMA-7.3 (¹⁸F-flotufolastat) is a high-affinity prostate-specific membrane antigen–targeted diagnostic radiopharmaceutical for PET imaging in patients with prostate cancer. Here, we report findings from the SPOTLIGHT study (NCT04186845), assessing the performance of ¹⁸F-flotufolastat PET/CT for identifying prostate-specific membrane antigen–positive lesions confirmed by standard of truth (SoT) in men with biochemical recurrence of prostate cancer and negative conventional imaging at baseline. Methods: Men with biochemical recurrence received 296 MBq of ¹⁸F-flotufolastat intravenously and then underwent PET/CT 50–70 min later. ¹⁸F-flotufolastat PET/CT findings were evaluated by 3 masked central readers and verified using histopathology or follow-up confirmatory imaging (CT, MRI, bone scan, or ¹⁸F-fluciclovine PET/CT) as the SoT. The present analysis evaluated all patients who had negative conventional imaging at baseline, underwent ¹⁸F-flotufolastat PET/CT, and had SoT verification by histopathology or follow-up confirmatory imaging to report detection rate (DR), which is the number of patients with at least 1 PET-positive lesion, divided by the number of evaluable patients, and verified DR (VDR), which is the proportion of patients with at least 1 true-positive lesion as verified by SoT, of all patients scanned (PET-positive and PET-negative scans). DR and VDR were calculated and stratified according to prior therapy. Majority read data (agreement between ≥2 readers) are reported. Results: In total, 171 patients with negative baseline conventional imaging and SoT by histopathology or post-PET confirmatory imaging were evaluated. By majority read, the overall ¹⁸F-flotufolastat DR among these patients was 95% (163/171; 95% CI, 91.0%–98.0%), and 110 of 171 of these patients had at least 1 true-positive lesion identified (VDR, 64%; 95% CI, 56.7%–71.5%). In the postprostatectomy group (133/171), 8.3% of patients had at least 1 true-positive lesion in the prostate bed, 28% in pelvic lymph nodes, and 35% in other sites. Among those who had received radiotherapy (36/171), 50% of patients had true-positive detections in the prostate, 8.3% in pelvic lymph nodes, and 36% in other sites. Conclusion: ¹⁸F-flotufolastat frequently identified true-positive prostate cancer lesions in patients with negative conventional imaging. ¹⁸F-flotufolastat may help to better define sites of disease recurrence and inform salvage therapy decisions than does conventional imaging, potentially leading to improved outcomes.

¹⁸ F-rhPSMA-7.3 ( ¹⁸ F-flotufolastat) 是一种高亲和力前列腺特异性膜抗原靶向诊断放射性药物，用于前列腺癌患者的 PET 成像。在这里，我们报告 SPOTLIGHT 研究 (NCT04186845) 的结果，该研究评估了¹⁸ F-flotufolastat PET/CT 在前列腺癌生化复发男性中识别经真实标准 (SoT) 证实的前列腺特异性膜抗原阳性病变的性能和基线时的阴性常规成像。方法：生化复发的男性静脉注射 296 MBq ¹⁸ F-flotufolastat，50-70 分钟后接受 PET/CT。 ¹⁸ F-氟洛司他 PET/CT 结果由 3 名蒙面中心阅片员进行评估，并使用组织病理学或后续验证性成像（CT、MRI、骨扫描或¹⁸ F-氟昔洛素 PET/CT）作为 SoT 进行验证。本分析评估了所有基线时常规影像学阴性、接受¹⁸ F-氟洛司他 PET/CT 并通过组织病理学或后续确认影像学进行 SoT 验证以报告检出率 (DR) 的患者，即患有以下疾病的患者数量：至少 1 个 PET 阳性病灶，除以可评估患者数量和经验证的 DR (VDR)，即所有扫描患者（PET 阳性）中经 SoT 验证至少有 1 个真阳性病灶的患者比例和 PET 阴性扫描）。根据既往治疗计算并分层 DR 和 VDR。报告大多数阅读数据（≥2 名读者之间的协议）。结果：总共对 171 名基线常规成像和组织病理学或 PET 后证实成像 SoT 呈阴性的患者进行了评估。 根据大多数读数，这些患者中¹⁸ F-flotufolastat 的总体 DR 为 95%（163/171；95% CI，91.0%–98.0%），其中 171 名患者中有 110 名至少识别出 1 个真阳性病变（ VDR，64%；95% CI，56.7%–71.5%）。在前列腺切除术后组 (133/171)，8.3% 的患者在前列腺床中至少有 1 个真阳性病变，28% 在盆腔淋巴结中，35% 在其他部位。在接受放射治疗的患者中（36/171），50%的患者前列腺检测为真阳性，8.3%的患者盆腔淋巴结检测为真阳性，36%的患者其他部位检测为真阳性。结论： ¹⁸ F-flotufolastat 经常在常规影像阴性的患者中发现真阳性前列腺癌病灶。与传统成像相比， ¹⁸ F-flotufolastat 可能有助于更好地确定疾病复发部位并为挽救治疗决策提供信息，从而可能改善结果。