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Using CD69 PET Imaging to Monitor Immunotherapy-Induced Immune Activation.

Kimberly J Edwards1, Bryan Chang1, Hasan Babazada1

  • 1Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.

Cancer Immunology Research
|July 21, 2022
PubMed
Summary

A novel PET imaging probe targeting CD69, an immune cell activation marker, shows promise for early assessment of immunotherapy response in solid tumors. This tool could predict patient response to immune checkpoint inhibitors (ICI).

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Area of Science:

  • Immunology
  • Molecular Imaging
  • Oncology

Background:

  • Immune checkpoint inhibitors (ICI) show limited efficacy in solid tumors, necessitating early response assessment tools.
  • Current methods lack precision for predicting patient response to immunotherapies.
  • CD69 is an early activation marker on cytotoxic T cells and NK cells, indicating immune cell activity.

Purpose of the Study:

  • To develop and validate a PET imaging probe for early assessment of immunotherapy response.
  • To evaluate CD69 as a biomarker for immune cell activation in response to cancer immunotherapy.
  • To investigate the utility of [89Zr]-DFO-H1.2F3 PET imaging in a preclinical immunotherapy model.

Main Methods:

  • Radiolabeling of a CD69 monoclonal antibody (mAb), H1.2F3, with Zirconium-89 (89Zr).
  • In vitro studies using primary mouse T cells to assess CD69 expression changes.
  • In vivo PET imaging in a syngeneic tumor immunotherapy model, followed by ex vivo analyses (biodistribution, autoradiography, IHC).

Main Results:

  • [89Zr]-DFO-H1.2F3 successfully detected CD69 expression changes on activated T cells in vitro (15-fold increase).
  • PET imaging revealed higher probe uptake in tumors of ICI-responsive mice compared to nonresponsive and untreated groups.
  • Ex vivo analyses confirmed in vivo PET findings, demonstrating sensitive detection of immune cell activation.

Conclusions:

  • CD69 PET imaging using [89Zr]-DFO-H1.2F3 can sensitively quantify immune cell activation.
  • This approach holds potential for predicting therapeutic immune responses to novel immunotherapies.
  • The developed PET probe could aid in early response assessment for cancer immunotherapies.