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Updated: Jun 22, 2026
Establishing Intracranial Brain Tumor Xenografts With Subsequent Analysis of Tumor Growth and Response to Therapy using Bioluminescence Imaging
Published on: July 13, 2010
Immunoimaging of CXCR4 expression in brain tumor xenografts using SPECT/CT
Sridhar Nimmagadda1, Mrudula Pullambhatla, Martin G Pomper
1Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, Maryland, USA.
Unlabelled:
Chemokine receptor 4 (CXCR4) is expressed in a variety of cancers, including breast, brain, ovarian, and prostate. CXCR4-CXCL12 interactions are critical for tumor development, growth, and metastasis. Compared with normal tissue, neoplastic tissue (including metastases) expresses high levels of CXCR4. Previous clinical and preclinical observations suggest that CXCR4 levels could be used as a predictive marker of metastatic potential. Here we report the results of SPECT/CT of CXCR4 expression levels in experimental brain tumors using (125)I-labeled anti-CXCR4 monoclonal antibodies (mAbs).
Methods:
hCXCR4 antibody 12G5 and control IgG(2A) antibody were radiolabeled. Radio-mAbs were obtained in 40%-60% yield, with 1.4-1.9 MBq/microg specific radioactivities and greater than 95% purity. Severe combined immunodeficient mice harboring U87 xenografts were used for ex vivo biodistribution and imaging studies. Surface CXCR4 expression levels on U87 tumor-derived cells were analyzed by flow cytometry.
Results:
Biodistribution and imaging studies showed a specific accumulation of (125)I-12G5 in U87 tumors, with tumor-to-muscle uptake ratios reaching 15 +/- 3 at 48 h after injection. The tumor-to-tumor uptake ratio for (125)I-12G5 and (125)I-IgG(2A) was 2.5 at 48 h after injection. Flow cytometry analysis of tumor-derived cells showed a 2- to 7-fold increase in CXCR4 expression relative to inoculums, accounting for the high mAb uptake observed in the tumors.
Conclusion:
Our data demonstrate the feasibility of imaging CXCR4 expression in experimental brain tumors. The elevated CXCR4 levels observed may have been, in part, due to the hypoxic tumor microenvironment.
Insights
Imaging chemokine receptor 4 (CXCR4) in experimental brain tumors is feasible. Elevated CXCR4 levels, potentially due to hypoxia, were successfully visualized using radiolabeled antibodies, indicating its role in tumor progression.
Area of Science:
- Oncology
- Molecular Imaging
- Biochemistry
Background:
- Chemokine receptor 4 (CXCR4) is crucial for tumor development and metastasis across various cancers.
- High CXCR4 expression in neoplastic tissue suggests its potential as a predictive marker for metastatic potential.
- CXCR4-CXCL12 interactions play a significant role in tumor progression and growth.
Purpose of the Study:
- To assess the feasibility of imaging CXCR4 expression in experimental brain tumors.
- To evaluate the use of radiolabeled anti-CXCR4 monoclonal antibodies for SPECT/CT imaging.
- To correlate CXCR4 expression levels with tumor characteristics in vivo.
Main Methods:
- Radiolabeling of anti-CXCR4 (12G5) and control IgG(2A) antibodies with Iodine-125 ((125)I).
- SPECT/CT imaging and ex vivo biodistribution studies in severe combined immunodeficient mice bearing U87 xenografts.
- Flow cytometry analysis of CXCR4 expression on tumor-derived cells.
Main Results:
- Specific accumulation of (125)I-12G5 in U87 brain tumors with high tumor-to-muscle uptake ratios (15 ± 3 at 48 h).
- Demonstrated a 2.5-fold higher tumor-to-tumor uptake ratio for (125)I-12G5 compared to control IgG(2A).
- Flow cytometry confirmed a 2- to 7-fold increase in CXCR4 expression on tumor cells.
Conclusions:
- SPECT/CT imaging of CXCR4 expression in experimental brain tumors is feasible.
- Elevated CXCR4 levels in tumors may be influenced by the hypoxic tumor microenvironment.
- CXCR4 imaging shows promise for assessing tumor characteristics and metastatic potential.
