Background: (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography/computed tomography (PET/CT) provides a readout of system xc−transport activity and has been used for cancer detection in clinical studies of different cancer types. As system xc−provides the rate-limiting precursor for glutathione biosynthesis, an abundant antioxidant, [18F]FSPG imaging may additionally provide important prognostic information. Here, we performed an analysis of [18F]FSPG radiotracer distribution between primary tumors, metastases, and normal organs from cancer patients. We further assessed the heterogeneity of [18F]FSPG retention between cancer types, and between and within individuals. Methods: This retrospective analysis of prospectively collected data compared [18F]FSPG PET/CT in subjects with head and neck squamous cell cancer (HNSCC,n= 5) and non-small-cell lung cancer (NSCLC,n= 10), scanned at different institutions. Using semi-automated regions of interest drawn around tumors and metastases, the maximum standardized uptake value (SUVmax), SUVmean, SUV standard deviation and SUVpeakwere measured. [18F]FSPG time–activity curves (TACs) for normal organs, primary tumors and metastases were subsequently compared to18F-2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT at 60 min post injection (p.i.). Results: The mean administered activity of [18F]FSPG was 309.3 ± 9.1 MBq in subjects with NSCLC and 285.1 ± 11.3 MBq in those with HNSCC. The biodistribution of [18F]FSPG in both cohorts showed similar TACs in healthy organs from cancer patients. There was no statistically significant overall difference in the average SUVmaxof tumor lesions at 60 min p.i. for NSCLC (8.1 ± 7.1) compared to HNSCC (6.0 ± 4.1;p= 0.29) for [18F]FSPG. However, there was heterogeneous retention between and within cancer types; the SUVmaxat 60 min p.i. ranged from 1.4 to 23.7 in NSCLC and 3.1–12.1 in HNSCC. Conclusion: [18F]FSPG PET/CT imaging from both NSCLC and HNSCC cohorts showed the same normal-tissue biodistribution, but marked tumor heterogeneity across subjects and between lesions. Despite rapid elimination through the urinary tract and low normal-background tissue retention, the diagnostic potential of [18F]FSPG was limited by variability in tumor retention. As [18F]FSPG retention is mediated by the tumor’s antioxidant capacity and response to oxidative stress, this heterogeneity may provide important insights into an individual tumor’s response or resistance to therapy.
背景：(4S)-4-(3-[18F]氟丙基)-L-谷氨酸（[18F]FSPG）正电子发射断层扫描/计算机断层扫描（PET/CT）可反映系统xc−转运活性，已在多种癌症类型的临床研究中用于肿瘤检测。由于系统xc−为谷胱甘肽（一种丰富的抗氧化剂）的生物合成提供限速前体，[18F]FSPG成像还可能提供重要的预后信息。本研究分析了癌症患者中原发肿瘤、转移灶与正常器官间[18F]FSPG放射性示踪剂的分布差异，并进一步评估了不同癌种间、个体间及病灶内[18F]FSPG摄取的异质性。 方法：这项对前瞻性收集数据的回顾性分析比较了在不同机构接受扫描的头颈部鳞状细胞癌（HNSCC，n=5）和非小细胞肺癌（NSCLC，n=10）患者的[18F]FSPG PET/CT影像。通过半自动勾画肿瘤及转移灶感兴趣区域，测量最大标准化摄取值（SUVmax）、平均标准化摄取值（SUVmean）、标准化摄取值标准差及峰值标准化摄取值（SUVpeak）。随后将正常器官、原发肿瘤及转移灶的[18F]FSPG时间-活度曲线与注射后60分钟的18F-氟代脱氧葡萄糖（[18F]FDG）PET/CT进行对比。 结果：NSCLC患者[18F]FSPG平均给药活度为309.3 ± 9.1 MBq，HNSCC患者为285.1 ± 11.3 MBq。两组患者正常器官的[18F]FSPG生物分布呈现相似的时间-活度曲线。注射后60分钟，NSCLC与HNSCC肿瘤病灶的平均SUVmax（分别为8.1 ± 7.1和6.0 ± 4.1）在[18F]FSPG成像中无统计学显著差异（p=0.29）。但不同癌种间及病灶内存在显著摄取异质性：NSCLC的SUVmax范围为1.4-23.7，HNSCC为3.1-12.1。 结论：NSCLC与HNSCC患者的[18F]FSPG PET/CT成像显示相同的正常组织生物分布，但不同患者及病灶间存在显著的肿瘤异质性。尽管[18F]FSPG经泌尿系统快速清除且正常本底组织摄取较低，但其诊断潜力受肿瘤摄取变异性的限制。由于[18F]FSPG摄取受肿瘤抗氧化能力及氧化应激反应介导，这种异质性可能为个体化肿瘤治疗反应或耐药机制提供重要参考。
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