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Galectin-3 (Gal-3) is a β-galactosidase binding protein that modulates various cellular processes including cell adhesion, and metastasis. We evaluated the tumor targeting and imaging properties of a galectin-3 binding peptide originally selected from bacteriophage display, in a mouse model of human breast carcinoma expressing galectin-3. A galectin-3 binding peptide, ANTPCGPYTHDCPVKR, was synthesized with a Gly-Ser-Gly (GSG) spacer and 1,4,7,10, tetraazacyclododecane-N,N’,N’’,N’’’-tetracetic acid (DOTA) or 4,11-bis(carboxymethyl)-1,4,8,11 tetrazabicyclo[6.6.2]hexadecane 4,11-diacetic acid (CB-TE2A), and radiolabeled with 64Cu. The synthesized peptides 64Cu-DO3A-(GSG)-ANTPCGPYTHDCPVKR (64Cu-DO3A- pep) and 64Cu-CB-TE2A-(GSG)-ANTPCGPYTHDCPVKR(64Cu-CB-TE2A-pep) demonstrated an IC50 value of 97 ± 6.7 nM and 130 ± 10.2 nM, respectively, to cultured MDA-MB-435 breast carcinoma cells in vitro in a competitive displacement binding study. The tumor tissue uptake in SCID mice bearing MDA-MB-435 tumors was 1.2 ± 0.18 %ID/g (64Cu-DO3A-pep) and 0.85 ± 0.0.9 %ID/g (64Cu-CB-TE2A-pep) at 30 min, respectively. While liver retention was moderate with both radiolabeled peptides the kidney retention was observed to be high. Radiation dose delivered to the tumor was estimated to be 42 mGy/mCi and 129 mGy/ mCi with CB-TE2A and DO3A peptides, respectively. Imaging studies demonstrated tumor uptake with both 64Cu-DO3A- and 64Cu-CB-TE2A-(GSG)-ANTPCGPYTHDCPVKR after 2 h post injection. These studies suggest that gal-3 binding peptide could be developed into a PET imaging agent for galectin-3-expressing breast tumors

Evaluation of 64Cu-DOTA- and 64Cu-CBTE2A-Galectin-3 Peptide as a PET Radiotracer for breast Carcinoma