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Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
Published on: March 25, 2020
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B7-H4 ImmunoPET Imaging Tracks Tumor-Associated Macrophage Changes in Prostate Cancer
Manoj Kumar1,2,3, Shashi B Singh1, Iryna Vasyliv1
1Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California 94305, United States.
Molecular Pharmaceutics
|October 22, 2025
Summary
Researchers developed a novel immunoPET tracer, [89Zr]Zr-DFO-2H9, for imaging B7-H4 expression in tumors and tumor-associated macrophages (TAMs). This tracer accurately reflects TAM levels and shows potential for monitoring immunotherapies.
Area of Science:
- Immunology
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- B7-H4 is an immune checkpoint molecule overexpressed in various cancers, linked to advanced disease and poor prognosis.
- Targeting B7-H4 offers a potential strategy for cancer immunotherapy and diagnostics.
- Noninvasive imaging of B7-H4 expression, particularly in tumor microenvironments, is crucial for treatment monitoring.
Purpose of the Study:
- To develop and characterize a novel immunoPET radiotracer targeting B7-H4 for in vivo imaging.
- To assess the tracer's ability to quantify B7-H4 expression in prostate cancer models.
- To evaluate the tracer's utility in monitoring therapeutic responses and immune cell infiltration, specifically tumor-associated macrophages (TAMs).
Main Methods:
- Generation of a [89Zr]-labeled anti-B7-H4 monoclonal antibody ([89Zr]Zr-DFO-2H9).
- In vitro validation of immunoreactivity and specificity.
- In vivo biodistribution and PET imaging studies in prostate cancer xenograft and syngeneic models.
- Assessment of tracer uptake following B7-H4 blockade and macrophage depletion.
Main Results:
- [89Zr]Zr-DFO-2H9 demonstrated high affinity and specificity for B7-H4 in vitro and showed favorable tumor uptake in vivo.
- PET imaging revealed significant signal reduction in tumors treated with B7-H4 blockade or macrophage depletion, indicating tracer sensitivity to these changes.
- Multiplexed immunofluorescence confirmed that TAMs were the primary source of the B7-H4-specific PET signal within the tumor stroma.
Conclusions:
- The developed [89Zr]Zr-DFO-2H9 immunoPET tracer is a promising tool for noninvasive detection of B7-H4 expression and TAMs in tumors.
- This radiotracer can potentially profile the tumor immune microenvironment and monitor the efficacy of macrophage-targeted immunotherapies.
- The findings support the clinical translation of [89Zr]Zr-DFO-2H9 for personalized cancer diagnostics and treatment evaluation.
