Importance Androgen receptor–signaling inhibitor (ARSi) drugs prolong life in metastatic castration–resistant prostate cancer (mCRPC), but such tumors eventually become resistant and progress. Comprehensive positron emission tomography/computed tomography (PET/CT) imaging using fluoro-2-D-deoxyglucose F 18 ([¹⁸F]-FDG) for glycolysis (Glyc) and fluorodihydrotestosterone F 18 ([¹⁸F]-FDHT) for androgen receptor (AR) expression determine heterogeneity of imaging phenotypes, which may be useful in distinguishing patients who will benefit from ARSi drugs from those who need alternative treatments.

Objective To test the hypothesis that PET/CT-based assessments of AR expression and glycolytic activity would reveal heterogeneity affecting prognosis.

Design, Setting, and Participants Between April 6, 2007, and October 4, 2012, patients with mCRPC underwent imaging with both [¹⁸F]-FDG and [¹⁸F]-FDHT at Memorial Sloan Kettering Cancer Center. The patients were naive to ARSi treatment with enzalutamide or abiraterone acetate and were referred during documented disease progression. Image-directed biopsy determined the presence or absence of prostate cancer at positive imaging sites.

Interventions PET/CT imaging was performed with [¹⁸F]-FDHT and [¹⁸F]-FDG; select individual lesions were biopsied to correlate imaging phenotype with histologic findings.

Main Outcomes and Measures All metabolically active lesions were interpreted as [¹⁸F]-FDHT-positive (AR₁) or [¹⁸F]-FDHT-negative (AR₀) and as [¹⁸F]-FDG-positive (Glyc₁) or [¹⁸F]-FDG-negative (Glyc₀). Correlation was performed with overall survival for both individual lesion imaging phenotype as well as patient-specific imaging phenotype.

Results The mean (SD) age of the 133 patients was 68 (8.6) years. Imaging phenotypes of 2405 PET/CT-positive lesions (median, 12.0 per patient) included 1713 (71.2%) AR₁Glyc₁, 386 (16.0%) AR₁Glyc₀, and 306 (12.7%) AR₀Glyc₁. On multivariate analysis, each phenotype had an independent negative impact effect on survival, most pronounced for AR₀Glyc₁ lesions (hazard ratio [HR], 1.11; 95% CI, 1.05-1.16; P < .001), followed by AR₁Glyc₁ lesions (HR, 1.05; 95% CI, 1.03-1.06; P < .001) and AR₁Glyc₀ lesions (HR, 1.03; 95% CI, 1.00-1.05; P = .048). When sorted by lesion type, 4 patient-specific groups emerged: (1) concordant, with all AR₁Glyc₁ (34 patients [25.6%]); (2) AR predominant, with AR₁Glyc₁ and varying numbers of AR₁Glyc₀ (33 [24.8%]); (3) Glyc predominant, with AR₁Glyc₁ and varying numbers of AR₀Glyc₁ (40 [30.1%]); and (4) mixed, with AR₁Glyc₁ plus a mixture of varying numbers of AR₁Glyc₀ and AR₀Glyc₁ (26 [19.5%]).

Conclusions and Relevance Heterogeneity of PET/CT imaging phenotype has clinical relevance on a lesion and individual patient level. With regard to mCRPC lesions, most express ARs, consistent with initial benefit of ARSi drugs. On a patient basis, 49% (groups 3 and 4) had at least 1 AR₀Glyc₁ lesion—the imaging phenotype with the most negative effect on survival, possibly due to ARSi resistance.

重要性 雄激素受体信号抑制剂 (ARSi) 药物可延长转移性去势抵抗性前列腺癌 (mCRPC) 的生命，但此类肿瘤最终会产生耐药性和进展。使用氟-2-D-脱氧葡萄糖 F 18 ([ ¹⁸ F]-FDG) 进行糖酵解 (Glyc) 和氟二氢睾酮 F 18 ([ ¹⁸ F]-FDHT) 进行雄激素的综合正电子发射断层扫描/计算机断层扫描 (PET/CT) 成像受体 (AR) 表达决定了成像表型的异质性，这可能有助于区分将从 ARSi 药物中受益的患者与需要替代治疗的患者。

目的 检验基于 PET/CT 评估 AR 表达和糖酵解活性将揭示影响预后的异质性的假设。

设计、设置和参与者 2007 年 4 月 6 日至 2012 年 10 月 4 日，mCRPC 患者在纪念斯隆凯特琳癌症中心接受了 [ 18 F]-FDG 和 [ 18 F] ^-FDHT成像^。患者未接受恩杂鲁胺或醋酸阿比特龙的 ARSi 治疗，并在记录的疾病进展期间被转诊。影像导向活检确定阳性成像部位是否存在前列腺癌。

^{使用 [ 18} F]-FDHT 和 [ ¹⁸ F] -FDG进行 PET/CT 成像；对选择的单个病变进行活检，以将成像表型与组织学发现相关联。

主要结果和措施 所有代谢活跃的病变都被解释为 [ ¹⁸ F]-FDHT 阳性 (AR ₁ ) 或 [ ¹⁸ F]-FDHT 阴性 (AR ₀ ) 和 [ ¹⁸ F]-FDG 阳性 (Glyc ₁ )或 [ ¹⁸ F]-FDG-阴性 (Glyc ₀ )。与个体病变成像表型以及患者特异性成像表型的总生存期相关。

结果 133 例患者的平均 (SD) 年龄为 68 (8.6) 岁。2405 个 PET/CT 阳性病灶（中位数，每名患者 12.0 个）的影像表型包括 1713 个（71.2%）AR ₁ Glyc ₁、386 个（16.0%）AR ₁ Glyc ₀和 306 个（12.7%）AR ₀ Glyc ₁。在多变量分析中，每种表型对生存都有独立的负面影响，最明显的是 AR ₀ Glyc ₁病变（风险比 [HR]，1.11；95% CI，1.05-1.16；P  <  .001），其次是 AR ₁ Glyc ₁病变（HR，1.05；95% CI，1.03-1.06；P  <  .001）和 AR_{1 个}Glyc ₀病变（HR，1.03；95% CI，1.00-1.05；P  = .048）。当按病变类型分类时，出现了 4 个患者特异性组：（1）与所有 AR ₁ Glyc ₁一致（34 名患者 [25.6%]）；(2) AR 为主，AR ₁ Glyc ₁和不同数量的 AR ₁ Glyc ₀ (33 [24.8%])；(3) Glyc 为主，AR ₁ Glyc ₁和不同数量的 AR ₀ Glyc ₁ (40 [30.1%])；(4) 混合，与 AR ₁ Glyc ₁加上不同数量的 AR ₁ Glyc _{0的混合物}和 AR ₀ Glyc ₁ (26 [19.5%])。

结论和相关 性 PET/CT 成像表型的异质性在病变和个体患者水平上具有临床相关性。对于 mCRPC 病变，大多数表达 AR，这与 ARSi 药物的初始益处一致。在患者基础上，49%（第 3 组和第 4 组）至少有 1 个 AR ₀ Glyc ₁病变——对生存率影响最大的成像表型，可能是由于 ARSi 抗性。