在转移性去势抵抗性前列腺癌 (mCRPC) 中，一些患者在正电子发射断层扫描 (PET) 扫描中显示肿瘤病灶中 PSMA 表达低/缺失，表明异质性以及对 PSMA-RLT（放射性配体治疗）无反应的风险增加。对癌症相关成纤维细胞和葡萄糖摄取进行成像可能会进一步表征 mCRPC 患者的肿瘤异质性。在这里，我们的目的是评估肿瘤异质性及其对使用 [68Ga]Ga-FAPI-46、2-[18F]FDG 和 [68Ga]Ga-/[18F]F- 评估 PSMA-RLT 的 mCRPC 患者治疗的潜在影响PSMA-11/-1007 PET。晚期进展性 mCRPC 患者接受临床 [68Ga]Ga-/[18F]F-PSMA-11/-1007、2-[18F]FDG 和 [68Ga]Ga-FAPI-46 PET /CT 评估 PSMA 导向的 RLT 治疗。在每个病变/区域的基础上比较肿瘤检测/半定量参数。定义了两种表型：混合表型的标准为：(a) 淋巴结转移灶 ≥ 2.5 cm、任何实体器官转移灶 ≥ 1.0 cm 或具有软组织成分的骨转移灶 ≥ 1.0 cm 的 PSMA 阴性结果，(b) 低[68Ga]Ga-/[18F]F-PSMA-11/-1007 摄取和/或 (c) 所有放射性配体的平衡肿瘤摄取。如果不满足标准，则分配 PSMA 显性表型。 在 10 名患者中，所有成像方式均检测到 472 个病变（miTNM 区域：M1b：327（69.3%）、M1a：95（20.1%）、N1：26（ 5.5%），M1c：18（3.8%），T：5（1.1%）和Tr：1（0.2%）[68Ga]Ga-/[18F]F-PSMA-11/-1007（n = 453）。 96.0%)) 的检出率最高，其次是 [68Ga]Ga-FAPI-46 (n = 268 (56.8%))/2-[ 18F]FDG (n = 241 (51.1%)) 半定量摄取最高。对于 [68Ga]Ga-/[18F]F-PSMA-11/-1007（平均 SUVmax（四分位距）：22.7 (22.5)，对比 [68Ga]Ga-FAPI-46 (7.7 (3.7)) 和 2- [18F]FDG（6.8（4.7））。七/三名患者被回顾性分配为 PSMA 显性/混合表型，接受 [177Lu]Lu-PSMA-617 RLT 并回顾性分配的患者的中位总生存期显着更长。到 PSMA 主导表型（19.7 个月与 9.3 个月）。通过全身成像，我们确定了 mCRPC 和潜在成像表型的相当大的患者间和患者内异质性。在摄取和肿瘤检测方面，[68Ga]Ga-/[18F]F-PSMA-11/-1007优于[68Ga]Ga-FAPI-46和2-[18F]FDG，而后两者相当。根据临床决策接受 [177Lu]Lu-PSMA-617 RLT 的患者总体生存期更长，并且可以被分配到 PSMA 显性表型。© 2024。作者。

In metastatic castration-resistant prostate cancer (mCRPC), some patients show low/absent PSMA expression in tumour lesions on positron emission tomography (PET) scans, indicating heterogeneity and heightened risk of non-response to PSMA-RLT (radioligand therapy). Imaging cancer-associated fibroblasts and glucose uptake may further characterise tumour heterogeneity in mCRPC patients. Here, we aimed to evaluate tumour heterogeneity and its potential implications for management in mCRPC patients assessed for PSMA-RLT using [68Ga]Ga-FAPI-46, 2-[18F]FDG and [68Ga]Ga-/[18F]F-PSMA-11/-1007 PET.Patients with advanced, progressive mCRPC underwent clinical [68Ga]Ga-/[18F]F-PSMA-11/-1007, 2-[18F]FDG and [68Ga]Ga-FAPI-46 PET/CT to evaluate treatment with PSMA-directed RLT. Tumour detection/semiquantitative parameters were compared on a per-lesion/-region basis. Two phenotypes were defined: Criteria for the mixed phenotype were: (a) PSMA-negative findings for lymph node metastases ≥ 2.5 cm, any solid organ metastases ≥ 1.0 cm, or bone metastases with soft tissue component ≥ 1.0 cm, (b) low [68Ga]Ga-/[18F]F-PSMA-11/-1007 uptake and/or (c) balanced tumour uptake of all radioligands. The PSMA-dominant phenotype was assigned if the criteria were not met.In ten patients, 472 lesions were detected on all imaging modalities (miTNM regions: M1b: 327 (69.3%), M1a: 95 (20.1%), N1: 26 (5.5%), M1c: 18 (3.8%), T: 5 (1.1%) and Tr: 1 (0.2%). [68Ga]Ga-/[18F]F-PSMA-11/-1007 (n = 453 (96.0%)) demonstrates the highest detection rate, followed by [68Ga]Ga-FAPI-46 (n = 268 (56.8%))/2-[18F]FDG (n = 241 (51.1%)). Semiquantitative uptake was highest for [68Ga]Ga-/[18F]F-PSMA-11/-1007 (mean SUVmax (interquartile range): 22.7 (22.5), vs. [68Ga]Ga-FAPI-46 (7.7 (3.7)) and 2-[18F]FDG (6.8 (4.7)). Seven/three patients were retrospectively assigned to the PSMA-dominant/mixed phenotype. Median overall survival was significantly longer for patients who underwent [177Lu]Lu-PSMA-617 RLT and were retrospectively assigned to the PSMA-dominant phenotype (19.7 vs. 9.3 months).Through whole-body imaging, we identify considerable inter- and intra-patient heterogeneity of mCRPC and potential imaging phenotypes. Regarding uptake and tumour detection, [68Ga]Ga-/[18F]F-PSMA-11/-1007 was superior to [68Ga]Ga-FAPI-46 and 2-[18F]FDG, while the latter two were comparable. Patients who underwent [177Lu]Lu-PSMA-617 RLT based on clinical-decision making had a longer overall survival and could be assigned to the PSMA-dominant phenotype.© 2024. The Author(s).