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¹¹¹In-Labeled Galectin-3–Targeting Peptide as a SPECT Agent for Imaging Breast Tumors

¹ Department of Biochemistry, University of Missouri, Columbia, Missouri; and ² Research Service, Harry S Truman Veterans Memorial Hospital, Columbia, Missouri

Correspondence: For correspondence or reprints contact: Susan L. Deutscher, Department of Biochemistry, 117 Schweitzer Hall, 1 Hospital Dr., Columbia, MO 65211. E-mail: deutschers{at}missouri.edu

Galectin-3 is a member of the galectin family of β-galactoside–binding animal lectins. Galectin-3 is overexpressed in a wide range of neoplasms and is associated with tumor growth and metastases. Given this fact, radiolabeled galectin-3–targeting molecules may be useful for the noninvasive imaging of tumors expressing galectin-3, as well as for targeted radionuclide therapy. In this study, the tumor cell–targeting and SPECT properties of a galectin-3–avid peptide identified from bacteriophage display were evaluated in human breast carcinoma cells and in human breast tumor–bearing mice. Methods: The galectin-3–avid peptide G3-C12 (ANTPCGPYTHDCPVKR) was synthesized with a Gly-Ser-Gly (GSG) linker at the amino terminus. After conjugation with 1,4,7,10-tetra-azacyclododecane-N,N',N''N'''-tetraacetic acid (DOTA), the peptide was labeled with ¹¹¹In. The radiochemical purity and stability of the compound was assessed by high-performance liquid chromatography. MDA-MB-435 human breast carcinoma cells expressing galectin-3 were used to characterize the in vitro binding properties of the radiolabeled compound. SCID mice bearing MDA-MB-435 xenografts were used as an in vivo model for biodistribution and imaging studies with the ¹¹¹In-labeled peptide. Results: ¹¹¹In-DOTA(GSG)-G3-C12 bound specifically to galectin-3–expressing MDA-MB-435 cells. The radiolabeled peptide was stable in serum and was found intact in excreted urine for at least 1 h. Competitive binding experiments indicated that the radiolabeled peptide exhibited an inhibitory concentration of 50% of 200.00 ± 6.70 nM for cultured breast carcinoma cells. In vivo biodistribution studies revealed that tumor uptake was 1.2 ± 0.24, 0.75 ± 0.05, and 0.6 ± 0.04 (mean ± SD) percentage injected dose per gram at 30 min, 1.0 h, and 2.0 h after injection of the radiotracer, respectively. SPECT/CT studies with ¹¹¹In-DOTA(GSG)-G3-C12 showed excellent tumor uptake and contrast in the tumor-bearing mice. Specificity of peptide binding was demonstrated by successful blocking (52%) of in vivo tumor uptake of ¹¹¹In-DOTA(GSG)-G3-C12 in the presence of its nonradiolabeled counterpart at 2 h after injection. Conclusion: This study demonstrated the successful use of a new radiolabeled peptide for the noninvasive imaging of galectin-3–positive breast tumors. This peptide may be a promising candidate for future clinical applications.

Key Words: peptide • phage • galectin-3 • imaging • breast cancer

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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