Immunoimaging of CXCR4 Expression in Brain Tumor Xenografts Using SPECT/CT
Open Access
- 12 June 2009
- journal article
- Published by Society of Nuclear Medicine in Journal of Nuclear Medicine
- Vol. 50 (7), 1124-1130
- https://doi.org/10.2967/jnumed.108.061325
Abstract
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 125I-labeled anti-CXCR4 monoclonal antibodies (mAbs). Methods: hCXCR4 antibody 12G5 and control IgG2A antibody were radiolabeled. Radio-mAbs were obtained in 40%–60% yield, with 1.4–1.9 MBq/μg 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 125I-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 125I-12G5 and 125I-IgG2A 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.This publication has 37 references indexed in Scilit:
- Antibodies and Antimatter: The Resurgence of Immuno-PETJournal of Nuclear Medicine, 2008
- Translating an Antagonist of Chemokine Receptor CXCR4: From Bench to BedsideClinical Cancer Research, 2008
- PREFERENTIAL EXPRESSION OF CHEMOKINE RECEPTOR CXCR4 BY HIGHLY MALIGNANT HUMAN GLIOMAS AND ITS ASSOCIATION WITH POOR PATIENT SURVIVALNeurosurgery, 2007
- A Significant Correlation between Nuclear CXCR4 Expression and Axillary Lymph Node Metastasis in Hormonal Receptor Negative Breast CancerAnnals of Surgical Oncology, 2007
- Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumorsNuclear Medicine and Biology, 2006
- Systemic anti-hepatocyte growth factor monoclonal antibody therapy induces the regression of intracranial glioma xenografts.Clinical Cancer Research, 2006
- CXCR4 expression mediates glioma cell invasivenessOncogene, 2006
- The role of CXCR4 receptor expression in breast cancer: a large tissue microarray studyBreast Cancer Research and Treatment, 2005
- Effect of Screening and Adjuvant Therapy on Mortality from Breast CancerThe New England Journal of Medicine, 2005
- Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu OncogeneScience, 1987