Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade is effective in a subset of patients with several tumor types, but predicting patient benefit using approved diagnostics is inexact, as some patients with PD-L1-negative tumors also show clinical benefit^1,2. Moreover, all biopsy-based tests are subject to the errors and limitations of invasive tissue collection^3-11. Preclinical studies of positron-emission tomography (PET) imaging with antibodies to PD-L1 suggested that this imaging method might be an approach to selecting patients^12,13. Such a technique, however, requires substantial clinical development and validation. Here we present the initial results from a first-in-human study to assess the feasibility of imaging with zirconium-89-labeled atezolizumab (anti-PD-L1), including biodistribution, and secondly test its potential to predict response to PD-L1 blockade (ClinicalTrials.gov identifiers NCT02453984 and NCT02478099). We imaged 22 patients across three tumor types before the start of atezolizumab therapy. The PET signal, a function of tracer exposure and target expression, was high in lymphoid tissues and at sites of inflammation. In tumors, uptake was generally high but heterogeneous, varying within and among lesions, patients, and tumor types. Intriguingly, clinical responses in our patients were better correlated with pretreatment PET signal than with immunohistochemistry- or RNA-sequencing-based predictive biomarkers, encouraging further development of molecular PET imaging for assessment of PD-L1 status and clinical response prediction.

中文翻译：

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89Zr-atezolizumab成像作为评估癌症对PD-L1阻滞的临床反应的一种非侵入性方法。

程序性细胞死亡蛋白-1 /配体-1（PD-1 / PD-L1）阻断剂在具有多种肿瘤类型的部分患者中有效，但由于某些PD-L1患者无法通过批准的诊断方法来预测患者获益阴性肿瘤也显示临床获益^1,2。此外，所有基于活检的检查均受侵入性组织收集^3-11的错误和限制。对PD-L1抗体进行正电子发射断层扫描（PET）成像的临床前研究表明，这种成像方法可能是选择患者的一种方法^12,13。但是，这种技术需要大量的临床开发和验证。在这里，我们介绍了一项首次人类研究的初步结果，该研究评估了用锆89标记的atezolizumab（anti-PD-L1）成像的可行性，包括生物分布，其次测试了其预测PD-L1反应的潜力。封锁（ClinicalTrials.gov标识符NCT02453984和NCT02478099）。我们在开始atezolizumab治疗之前对22种患者进行了三种肿瘤类型的成像。PET信号是示踪剂暴露和靶标表达的函数，在淋巴组织和炎症部位均较高。在肿瘤中，摄取通常很高，但异质性不同，在病变，患者和肿瘤类型之间和之中都有所不同。有趣的是