High sensitivity imaging tools could provide a more holistic view of target antigen expression to improve the identification of patients who might benefit from cancer immunotherapy. We developed for immunoPET a novel recombinant human IgG1 (termed C4) that potently binds an extracellular epitope on human and mouse PD-L1 and radiolabeled the antibody with zirconium-89. Small animal PET/CT studies showed that ⁸⁹Zr-C4 detected antigen levels on a patient derived xenograft (PDX) established from a non-small-cell lung cancer (NSCLC) patient before an 8-month response to anti-PD-1 and anti-CTLA4 therapy. Importantly, the concentration of antigen is beneath the detection limit of previously developed anti-PD-L1 radiotracers, including radiolabeled atezolizumab. We also show that ⁸⁹Zr-C4 can specifically detect antigen in human NSCLC and prostate cancer models endogenously expressing a broad range of PD-L1. ⁸⁹Zr-C4 detects mouse PD-L1 expression changes in immunocompetent mice, suggesting that endogenous PD-1/2 will not confound human imaging. Lastly, we found that ⁸⁹Zr-C4 could detect acute changes in tumor expression of PD-L1 due to standard of care chemotherapies. In summary, we present evidence that low levels of PD-L1 in clinically relevant cancer models can be imaged with immunoPET using a novel recombinant human antibody.

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使用ImmunoPET对PD-L1表达进行成像

高灵敏度的成像工具可以提供靶抗原表达的更全面的视图，以改善对可能受益于癌症免疫疗法的患者的识别。我们为immunoPET开发了一种新型重组人IgG1（称为C4），可有效结合人和小鼠PD-L1上的细胞外表位，并用锆89放射性标记抗体。小型动物PET / CT研究显示，在对抗PD-1和PD的8个月反应之前，有^89个Zr-C4检测到了来自非小细胞肺癌（NSCLC）患者的患者异种移植物（PDX）的抗原水平。抗CTLA4治疗。重要的是，抗原浓度低于先前开发的抗PD-L1放射性示踪剂（包括放射性标记的atezolizumab）的检测限。我们还显示了⁸⁹Zr-C4可以特异性检测人类NSCLC和内源性表达广泛PD-L1的前列腺癌模型中的抗原。⁸⁹ Zr-C4可检测具有免疫功能的小鼠中的小鼠PD-L1表达变化，这表明内源性PD-1 / 2不会混淆人类成像。最后，我们发现⁸⁹ Zr-C4可以检测出由于标准的护理化学疗法而导致的PD-L1肿瘤表达的急性变化。总而言之，我们提供了证据，可以使用新型重组人抗体用immunoPET对临床相关癌症模型中低水平的PD-L1进行成像。