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Immunoimaging of CXCR4 Expression in Brain Tumor Xenografts Using SPECT/CT

Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, Maryland

Correspondence: For correspondence or reprints contact: Martin G. Pomper, Johns Hopkins Medical Institutions, 1550 Orleans St., 492 CRB II, Baltimore, MD 21231. E-mail: mpomper{at}jhmi.edu

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 IgG_2A 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-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.

Key Words: hypoxia • tumor microenvironment • molecular imaging • xenograft • chemokine

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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