Intrapatient intermetastatic heterogeneity (IIH) has been demonstrated in metastatic castration-resistant prostate cancer (mCRPC) patients and is of the utmost importance for radiopharmaceutical therapy (RPT) eligibility. This study was designed to determine the prevalence of IIH and RPT eligibility in mCRPC patients through a triple-tracer PET imaging strategy. Methods: This was a multisite prospective observational study in which mCRPC patients underwent both ¹⁸F-FDG and ⁶⁸Ga-prostate-specific membrane antigen (PSMA)–617 PET/CT scans. A third scan with ⁶⁸Ga-DOTATATE, a potential biomarker of neuroendocrine differentiation, was performed if an ¹⁸F-FDG–positive/⁶⁸Ga-PSMA–negative lesion was found. Per-tracer lesion positivity was defined as having an uptake at least 50% above that of the liver. IIH prevalence was defined as the percentage of participants having at least 2 lesions with discordant features on multitracer PET. Results: IIH was observed in 81 patients (82.7%), and at least 1 ¹⁸F-FDG–positive/⁶⁸Ga-PSMA–negative lesion was found in 45 patients (45.9%). Of the 37 participants who also underwent ⁶⁸Ga-DOTATATE PET/CT, 6 (16.2%) had at least 1 ⁶⁸Ga-DOTATATE–positive lesion. In total, 12 different combinations of lesion imaging phenotypes were observed. On the basis of our prespecified criteria, 52 (53.1%) participants were determined to be eligible for PSMA RPT, but none for DOTATATE RPT. Patients with IIH had a significantly shorter median overall survival than patients without IIH (9.5 mo vs. not reached; log-rank P = 0.03; hazard ratio, 2.7; 95% CI, 1.1–6.8). Conclusion: Most mCRPC patients showed IIH, which was associated with shorter overall survival. On the basis of a triple-tracer PET approach, multiple phenotypic combinations were found. Correlation of these imaging phenotypes with genomics and treatment response will be relevant for precision medicine.

患者内部转移间异质性 （IIH） 已在转移性去势抵抗性前列腺癌 （mCRPC） 患者中得到证实，并且对于放射性药物治疗 （RPT） 资格至关重要。本研究旨在通过三重示踪剂 PET 成像策略确定 mCRPC 患者 IIH 和 RPT 合格率的患病率。方法：这是一项多中心前瞻性观察研究，其中 mCRPC 患者接受了 ¹⁸次 F-FDG 和 ⁶⁸次 Ga-前列腺特异性膜抗原 （PSMA）-617 次 PET/CT 扫描。如果发现 ¹⁸F-FDG 阳性/⁶⁸Ga-PSMA 阴性病灶，则使用 ⁶⁸Ga-DOTATATE（神经内分泌分化的潜在生物标志物）进行第三次扫描。每个示踪剂病灶阳性定义为摄取率至少比肝脏高 50%。IIH 患病率定义为在多示踪剂 PET 上至少有 2 个病变且特征不一致的参与者百分比。结果：在 81 例患者 （82.7%） 中观察到 IIH，在 45 例患者中至少发现 1 ¹⁸个 F-FDG 阳性/⁶⁸个 Ga-PSMA 阴性病灶 （45.9%）。在接受 ⁶⁸例 Ga-DOTATATE PET/CT 的 37 例参与者中，6 例 （16.2%） 至少有 1 ⁶⁸例 Ga-DOTATATE 阳性病变。总共观察到 12 种不同的病变成像表型组合。根据我们预先设定的标准，52 名 （53.1%） 参与者被确定为 PSMA RPT 合格，但没有人符合 DOTATATE RPT 的条件。IIH 患者的中位总生存期显著短于无 IIH 的患者 （9.5 个月 vs. 未达到;对数秩 P = 0.03;风险比，2.7;95% CI，1.1-6.8）。 结论：大多数 mCRPC 患者显示 IIH，这与较短的总生存期相关。在三重示踪剂 PET 方法的基础上，发现了多种表型组合。这些影像学表型与基因组学和治疗反应的相关性将与精准医学相关。