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Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Radiopharmaceuticals as Novel Immune System Tracers
Natalie A Ridge1, Anne Rajkumar-Calkins2, Stephanie O Dudzinski2
1Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Abstract:
Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigms for multiple cancers. However, ICI therapy often fails to generate measurable and sustained antitumor responses, and clinically meaningful benefits remain limited to a small proportion of overall patients. A major obstacle to development and effective application of novel therapeutic regimens is optimized patient selection and response assessment. Noninvasive imaging using novel immunoconjugate radiopharmaceuticals (immuno-positron emission tomography and immuno-single-photon emission computed tomography) can assess for expression of cell surface immune markers, such as programmed cell death protein ligand-1 (PD-L1), akin to a virtual biopsy. This emerging technology has the potential to provide clinicians with a quantitative, specific, real-time evaluation of immunologic responses relative to cancer burden in the body. We discuss the rationale for using noninvasive molecular imaging of the programmed cell death protein-1 and PD-L1 axis as a biomarker for immunotherapy and summarize the current status of preclinical and clinical studies examining PD-L1 immuno-positron emission tomography. The strategies described in this review provide insight for future clinical trials exploring the use of immune checkpoint imaging as a biomarker for both ICI and radiation therapy, and for the rational design of combinatorial therapeutic regimens.
Insights
Immune checkpoint inhibitors (ICIs) show promise but limited efficacy. Novel imaging techniques like PD-L1 immuno-PET offer a virtual biopsy for better patient selection and response assessment in cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Radiopharmaceuticals
Background:
- Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but benefit only a subset of patients.
- Optimizing patient selection and response assessment is crucial for improving ICI efficacy.
- Noninvasive imaging offers a potential solution for real-time evaluation of immune responses.
Purpose of the Study:
- To review the rationale and current status of noninvasive molecular imaging for assessing the PD-1/PD-L1 axis in cancer immunotherapy.
- To highlight the potential of PD-L1 immuno-PET as a biomarker for patient selection and response monitoring.
- To provide insights for future clinical trials and therapeutic regimen design.
Main Methods:
- Review of preclinical and clinical studies on PD-L1 immuno-positron emission tomography (immuno-PET).
- Discussion of immunoconjugate radiopharmaceuticals for assessing cell surface immune markers.
- Exploration of molecular imaging strategies for immune checkpoint biomarkers.
Main Results:
- Noninvasive immuno-PET can provide a quantitative, real-time assessment of PD-L1 expression, akin to a virtual biopsy.
- Immuno-PET has the potential to guide patient selection for ICI therapy.
- Current research indicates promising applications for PD-L1 immuno-PET in various cancers.
Conclusions:
- Immune checkpoint imaging, particularly PD-L1 immuno-PET, holds significant promise as a biomarker for immunotherapy.
- This technology can enhance patient stratification and enable personalized treatment strategies.
- Future research should focus on integrating immune imaging into clinical trials for ICI and combination therapies.
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