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

Mol Imaging Biol. 2020 Dec;22(6):1553-1561. doi: 10.1007/s11307-020-01527-3. Epub 2020 Aug 19.

Abstract

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.

Keywords: Cancer; Immune checkpoint inhibitor; Immunotherapy; Precision medicine; Predictive biomarker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / analysis*
  • B7-H1 Antigen / metabolism*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Kinetics
  • Mice
  • Molecular Weight
  • Neoplasms / pathology
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemistry*
  • Single-Chain Antibodies / chemistry
  • Tissue Distribution
  • Zirconium / chemistry

Substances

  • Antibodies
  • B7-H1 Antigen
  • CD274 protein, human
  • Radiopharmaceuticals
  • Single-Chain Antibodies
  • Zirconium