Theranostics 2011; 1:251-262. doi:10.7150/thno/v01p0251 This volume

Research Paper

PET imaging of CXCR4 using copper-64 labeled peptide antagonist

Orit Jacobson1, Ido D. Weiss2, Lawrence P. Szajek3, Gang Niu1, Ying Ma1, Dale O. Kiesewetter1, Joshua M. Farber2, Xiaoyuan Chen1, ✉

1. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland
2. Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland
3. Positron Emission Tomography Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland

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Jacobson O, Weiss ID, Szajek LP, Niu G, Ma Y, Kiesewetter DO, Farber JM, Chen X. PET imaging of CXCR4 using copper-64 labeled peptide antagonist. Theranostics 2011; 1:251-262. doi:10.7150/thno/v01p0251. Available from

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Expression of CXCR4 in cancer has been found to correlate with poor prognosis and resistance to chemotherapy. In this study we developed a derivative of the CXCR4 peptide antagonist, T140-2D, that can be labeled easily with the PET isotope copper-64, and thereby enable in vivo visualization of CXCR4 in tumors. T140 was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono (N-hydroxysuccinimide ester) (DOTA-NHS) to give T140-2D, which contains a DOTA molecule on each of the two lysine residues. 64Cu-T140-2D was evaluated in vitro by migration and binding experiments, and in vivo by microPET imaging and biodistribution, in mice bearing CXCR4-positive and CXCR4-negative tumor xenografts. T140-2D was labeled with copper-64 to give 64Cu-T140-2D in a high radiochemical yield of 86 ± 3% (not decay-corrected) and a specific activity of 0.28 - 0.30 mCi/µg (10.36 - 11.1 MBq/µg). 64Cu-T140-2D had antagonistic and binding characteristics to CXCR4 that were similar to those of T140. In vivo, 64Cu-T140-2D tended to bind to red blood cells and had to be used in a low specific activity form. In this new form 64Cu-T140-2D enabled specific imaging of CXCR4-positive, but not CXCR4-negative tumors. Undesirably, however, 64Cu-T140-2D also displayed high accumulation in the liver and kidneys. In conclusion, 64Cu-T140-2D was easily labeled and, in its low activity form, enabled imaging of CXCR4 in tumors. It had high uptake, however, in metabolic organs. Further research with imaging tracers targeting CXCR4 is required.

Keywords: T140 peptide, CXCR4 imaging, PET, copper-64