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

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 rigorous comparison to 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 tumor to normal tissue ratios were generally higher for (89)Zr-C4 scFv compared to (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.