Related Experiment Video
Updated: Feb 17, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Targeting CXCR4 with [68Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?
Constantin Lapa1, Stefan Kircher2, Andreas Schirbel1
1Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
Abstract:
C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [68Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [68Ga]Pentixafor-PET/CT. 2'-[18F]fluoro-2'-deoxy-D-glucose ([18F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up. Whereas [18F]FDG-PET depicted active lesions in all patients, [68Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [68Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed. In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.
Insights
[68Ga]Pentixafor positron emission tomography/computed tomography (PET/CT) imaging did not detect C-X-C motif chemokine receptor 4 (CXCR4) in malignant pleural mesothelioma patients. This suggests CXCR4 is largely absent, questioning its utility for diagnosis or therapy in this cancer.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiochemistry
Background:
- C-X-C motif chemokine receptor 4 (CXCR4) is implicated in tumor progression and metastasis across various cancers.
- Targeting CXCR4 is a potential strategy for cancer diagnosis and therapy.
- Malignant pleural mesothelioma is an aggressive cancer with limited treatment options.
Purpose of the Study:
- To evaluate the feasibility of CXCR4-directed imaging using [68Ga]Pentixafor-PET/CT in patients with malignant pleural mesothelioma.
- To assess the correlation between [68Ga]Pentixafor uptake and CXCR4 expression in pleural mesothelioma.
Main Methods:
- Six patients with malignant pleural mesothelioma underwent [68Ga]Pentixafor-PET/CT scans.
- Four patients also had [18F]FDG-PET/CT scans for comparison.
- Immunohistochemistry was performed on biopsy or surgical samples from all patients to determine CXCR4 expression.
- Histological analysis of nine additional mesothelioma samples was conducted.
Main Results:
- [18F]FDG-PET/CT identified active lesions in all patients where performed.
- [68Ga]Pentixafor-PET/CT showed only physiologic tracer distribution, with no positive lesions detected in any of the six patients.
- Immunohistochemistry results were consistent with the PET/CT findings, revealing no significant CXCR4 surface expression in the analyzed samples.
- This contrasts with previous studies suggesting CXCR4 expression in other cancers.
Conclusions:
- The study indicates a widespread absence of CXCR4 expression in malignant pleural mesothelioma.
- CXCR4-directed imaging with [68Ga]Pentixafor is not feasible for this indication.
- Confirmation of robust cell surface CXCR4 expression is crucial before considering it as a target for diagnosis or therapy in pleural mesothelioma.
More Related Videos
07:54Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019
07:41A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
