Purpose

The swell of new and diverse radiotracers to predict or monitor tumor response to cancer immunotherapies invites the opportunity for comparative studies to identify optimal platforms. To probe the significance of antibody format on image quality for PD-L1 imaging, we developed and studied the biodistribution of a library of antibodies based on the anti-PD-L1 IgG1 clone C4.

Procedure

A C4 minibody and scFv were cloned, expressed, and characterized. The antibodies were functionalized with desferrioxamine and radiolabeled with Zr-89 to enable a rigorous comparison with prior data collected using ⁸⁹Zr-labeled C4 IgG1. The biodistribution of the radiotracers was evaluated in C57Bl6/J or nu/nu mice bearing B16F10 or H1975 tumors, respectively, which are models that represent high and low tumor autonomous PD-L1 expression.

Results

The tumor uptake of the ⁸⁹Zr-C4 minibody was higher than ⁸⁹Zr-C4 scFv and equivalent to previous data collected using ⁸⁹Zr-C4 IgG1. However, the peak tumors to normal tissue ratios were generally higher for ⁸⁹Zr-C4 scFv compared with ⁸⁹Zr-C4 minibody and ⁸⁹Zr-IgG1. Moreover, an exploratory study showed that the rapid clearance of ⁸⁹Zr-C4 scFv enabled detection of endogenous PD-L1 on a genetically engineered and orthotopic model of hepatocellular carcinoma.

Conclusion

In summary, these data support the use of low molecular weight constructs for PD-L1 imaging, especially for tumor types that manifest in abdominal organs that are obstructed by the clearance of high molecular weight radioligands.

中文翻译：

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对等克隆抗体形式的分析表明使用低分子量 PET 放射性示踪剂测量 PD-L1 的作用。

目的

用于预测或监测肿瘤对癌症免疫疗法的反应的新型和多样化放射性示踪剂的激增为比较研究提供了确定最佳平台的机会。为了探究抗体格式对 PD-L1 成像图像质量的重要性，我们开发并研究了基于抗 PD-L1 IgG1 克隆 C4 的抗体库的生物分布。

程序

克隆、表达和表征了 C4 微型抗体和 scFv。这些抗体用去铁胺功能化并用 Zr-89 放射性标记，以便与使用⁸⁹ Zr 标记的 C4 IgG1收集的先前数据进行严格比较。分别在携带 B16F10 或 H1975 肿瘤的 C57Bl6/J 或 nu/nu 小鼠中评估放射性示踪剂的生物分布，这些模型代表高和低肿瘤自主 PD-L1 表达。

结果

⁸⁹ Zr-C4 微型抗体的肿瘤吸收率高于⁸⁹ Zr-C4 scFv，与之前使用⁸⁹ Zr-C4 IgG1收集的数据相当。然而，峰值的肿瘤与正常组织比通常更高为是⁸⁹ Zr的C4的scFv相比⁸⁹ Zr的C4微抗体和⁸⁹的Zr-IgG1的。此外，一项探索性研究表明，⁸⁹ Zr-C4 scFv的快速清除能够在肝细胞癌的基因工程和原位模型上检测到内源性 PD-L1。

结论

总之，这些数据支持使用低分子量构建体进行 PD-L1 成像，特别是对于腹部器官中因高分子量放射性配体清除而受阻的肿瘤类型。