An Analysis of Isoclonal Antibody Formats Suggests a Role for Measuring PD-L1 with Low Molecular Weight PET Radiotracers

• Published in: Molecular imaging and biology Vol. 22; no. 6; pp. 1553 - 1561
• Main Authors: Wei, Junnian, Wang, Yung-hua, Lee, Chia Yin, Truillet, Charles, Oh, David Y., Xu, Yichen, Ruggero, Davide, Flavell, Robert R., VanBrocklin, Henry F., Seo, Youngho, Craik, Charles S., Fong, Lawrence, Wang, Cheng-I, Evans, Michael J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2020; Springer Nature B.V
• Subjects: Antibodies; Cancer; Cancer immunotherapy; Comparative studies; Deferoxamine; Genetic engineering; Hepatocellular carcinoma; Image quality; Imaging; Immune checkpoint inhibitors; Immunoglobulin G; Immunotherapy; Liver cancer; Low molecular weights; Medicine; Medicine & Public Health; Molecular weight; Organs; PD-L1 protein; Radioactive tracers; Radioisotopes; Radiology; Research Article; Tumors; Zirconium isotopes; Immune checkpoint inhibitor; Precision medicine; Immunotherapy; Predictive biomarker; Cancer
• ISSN: 1536-1632; 1860-2002; 1860-2002
• DOI: 10.1007/s11307-020-01527-3

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 89 Zr-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 89 Zr-C4 minibody was higher than 89 Zr-C4 scFv and equivalent to previous data collected using 89 Zr-C4 IgG1. However, the peak tumors to normal tissue ratios were generally higher for 89 Zr-C4 scFv compared with 89 Zr-C4 minibody and 89 Zr-IgG1. Moreover, an exploratory study showed that the rapid clearance of 89 Zr-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.