alexa 111In-labeled galectin-3-targeting peptide as a SPECT agent for imaging breast tumors.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular Biomarkers & Diagnosis

Author(s): Kumar SR, Deutscher SL

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Abstract Galectin-3 is a member of the galectin family of beta-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 (111)In. 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 (111)In-labeled peptide. RESULTS: (111)In-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 (111)In-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 (111)In-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. This article was published in J Nucl Med and referenced in Journal of Molecular Biomarkers & Diagnosis

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