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Updated: Nov 26, 2025
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
PET imaging of immune checkpoint proteins in oncology
Alizée Bouleau1, Vincent Lebon1, Charles Truillet1
1Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 ORSAY, France.
Abstract:
Despite the remarkable clinical successes of immune checkpoint inhibitors (ICIs) in various advanced cancers, response is still limited to a subset of patients that generally exhibit tumoral expression of immune checkpoint (IC) proteins. Development of biomarkers assessing the expression of such ICs is therefore a major challenge nowadays to refine patient selection and improve therapeutic benefits. Positron emission tomography (PET) imaging using IC-targeted radiolabeled monoclonal antibodies (immunoPET) provides a non-invasive and whole-body visualization of in vivo IC biodistribution. As such, PET imaging of ICs may serve as a robust biomarker to predict and monitor responses to ICIs, complementing the existing immunohistochemical techniques. Besides monoclonal antibodies, other PET radioligand formats, ranging from antibody-derived fragments to small proteins, have gained increasing interest owing to their faster pharmacokinetics and enhanced imaging characteristics. We provide an overview of the various strategies investigated so far for PET imaging of ICs in preclinical and clinical studies, emphasizing their benefits and limitations. Moreover, we discuss various parameters to consider for designing optimized and best-suited PET radioligands.
Insights
ImmunoPET imaging visualizes immune checkpoints (ICs) non-invasively, offering a promising biomarker for predicting and monitoring responses to immune checkpoint inhibitors (ICIs) in cancer patients.
Area of Science:
- Oncology
- Immunology
- Radiochemistry
Background:
- Immune checkpoint inhibitors (ICIs) show success in advanced cancers but benefit a limited patient subset.
- Tumoral expression of immune checkpoint (IC) proteins is key for ICI response, necessitating better biomarkers for patient selection.
Purpose of the Study:
- To review current strategies for Positron Emission Tomography (PET) imaging of ICs.
- To evaluate the potential of immunoPET as a biomarker for predicting and monitoring ICI therapy.
Main Methods:
- Overview of preclinical and clinical studies utilizing IC-targeted radiolabeled antibodies (immunoPET) and other radioligand formats.
- Discussion of benefits, limitations, and design considerations for PET radioligands.
Main Results:
- ImmunoPET enables non-invasive, whole-body visualization of in vivo IC biodistribution.
- Alternative radioligand formats offer improved pharmacokinetics and imaging characteristics.
Conclusions:
- ImmunoPET serves as a robust biomarker, complementing immunohistochemistry for refining patient selection and improving therapeutic benefits of ICIs.
- Optimization of PET radioligands is crucial for enhanced clinical utility.
