Anti–programmed death 1 (PD-1) inhibitors are the standard of care for advanced gastroesophageal cancer. Although recommendations and approval by regulatory agencies are often based on programmed death ligand 1 (PD-L1) expression, pathologic assessments of PD-L1 status have several limitations. Single-site biopsies do not adequately capture disease heterogeneity within individual tumor lesions or among several lesions within the same patient, the PD-L1 combined positive score is a dynamic biomarker subject to evolution throughout a patient’s disease course, and repeated biopsies are invasive and not always feasible. Methods: This was a prospective pilot study of the PD-L1–targeting radiotracer, ¹⁸F-BMS-986229, with PET imaging (PD-L1 PET) in patients with gastroesophageal cancer. Patients were administered the ¹⁸F-BMS-986229 radiotracer intravenously at a dose of 370 MBq over 1–2 min and underwent whole-body PET/CT imaging 60 min later. The primary objective of this study was to evaluate the safety and feasibility of ¹⁸F-BMS-986229. The trial is registered with ClinicalTrials.gov (NCT04161781). Results: Between February 3, 2020, and February 2, 2022, 10 patients with gastroesophageal adenocarcinoma underwent PD-L1 PET. There were no adverse events associated with the ¹⁸F-BMS-986229 tracer, and imaging did not result in treatment delays; the primary endpoint was achieved. Radiographic evaluation of PD-L1 expression was concordant with pathologic assessment in 88% of biopsied lesions, and ¹⁸F-BMS-986229 uptake on PET imaging correlated with pathologic evaluation by the combined positive score (Spearman rank correlation coefficient, 0.64). Seventy-one percent of patients with ¹⁸F-BMS-986229 accumulation on PET imaging also had lesions without ¹⁸F-BMS-986229 uptake, highlighting the intrapatient heterogeneity of PD-L1 expression. Patients treated with frontline programmed death 1 inhibitors who had ¹⁸F-BMS-986229 accumulation in any lesions on PET imaging had longer progression-free survival than patients without tracer accumulation in any lesions (median progression-free survival, 28.4 vs. 9.9 mo), though the small sample size prevents any definitive conclusions. Conclusion: PD-L1 PET imaging was safe, feasible, and concordant with pathologic evaluation and offers a potential noninvasive tool to assess PD-L1 expression.

抗程序性死亡 1 (PD-1) 抑制剂是晚期胃食管癌的标准治疗方法。尽管监管机构的建议和批准通常基于程序性死亡配体 1 (PD-L1) 的表达，但 PD-L1 状态的病理评估存在一些局限性。单部位活检不能充分捕获单个肿瘤病变内或同一患者内多个病变之间的疾病异质性，PD-L1 组合阳性评分是一个动态生物标志物，在整个患者的病程中会发生演变，重复活检是侵入性的，而不是非侵入性的。总是可行的。方法：这是一项针对胃食管癌患者使用 PET 成像 (PD-L1 PET) 进行PD-L1 靶向放射性示踪剂¹⁸ F-BMS-986229的前瞻性试点研究。患者在 1-2 分钟内以 370 MBq 的剂量静脉注射¹⁸ F-BMS-986229 放射性示踪剂，并在 60 分钟后进行全身 PET/CT 成像。本研究的主要目的是评估¹⁸ F-BMS-986229 的安全性和可行性。该试验已在 ClinicalTrials.gov 注册（NCT04161781）。结果： 2020年2月3日至2022年2月2日期间，10例胃食管腺癌患者接受了PD-L1 PET检查。没有与¹⁸ F-BMS-986229 示踪剂相关的不良事件，成像也没有导致治疗延迟；达到了主要终点。 PD-L1 表达的放射学评估与 88% 活检病变的病理评估一致， PET 成像上¹⁸ F-BMS-986229 的摄取与综合阳性评分的病理评估相关（Spearman 等级相关系数，0.64）。PET 成像中¹⁸ F-BMS-986229 积聚的患者中有 71%也存在未摄取¹⁸ F-BMS-986229 的病变，这凸显了患者内 PD-L1 表达的异质性。使用一线程序性死亡 1 抑制剂治疗的患者，如果 PET 成像显示任何病灶内有¹⁸ F-BMS-986229 积聚，则其无进展生存期比任何病灶内没有示踪剂积聚的患者更长（中位无进展生存期，28.4 个月与 9.9 个月） ，尽管样本量较小，无法得出明确的结论。结论： PD-L1 PET显像安全、可行，与病理评估一致，为评估PD-L1表达提供了一种潜在的无创工具。