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Human epidermal growth factor receptor 2 (HER2) is overexpressed in several cancers. Today’s tumor targeting is receiving more attention due to its specificity to target receptor-dependent cancers. The aim of this study was to evaluate the  99m Tc-HYNIC-(tricine)-(Ser) 3 -LTVPWY peptide for tumor targeting and imaging with overexpression of HER2. HYNIC-(Ser) 3 -LTVPWY peptide was labeled with  99m Tc using tricine as a co-ligand at room temperature. Specific binding of this radiolabeled peptide was assessed on four cancer cell lines with different levels of HER2 receptor expression. Also the affinity of  99m Tc-HYNIC-(tricine)-(Ser) 3 -LTVPWY peptide to the HER2 receptor was evaluated in the SKOV-3 cell line. Biodistribution study of this radiolabeled peptide was performed in SKOV-3 tumor bearing nude mice. The HYNIC conjugated peptide was simply labeled with  99m Tc radionuclide with high labeling efficiency about 98±1% showing favorable stability in normal saline and human serum. In the presence of unlabeled peptide as competitor, the HER2 binding capacity of the radiolabeled peptide reduced (approximately five-fold). The K D  and B max  values were found 2.6±0.5 nM and (2.6±0.1)×10 6 , respectively. The tumor/muscle ratios for this radiotracer were determined 1.17±0.77, 1.15±0.32 and 2.65±0.32 at 1, 2 and 4 h after injection, respectively. Presaturation of HER2 receptors in SKOV-3 xenografted nude mice showed a reduction in the tumor/muscle ratio confirming  in vivo  specificity of the peptide. According to SPECT imaging, the tumor was visualized in mouse after 4 h postinjection of radiolabeled peptide.  99m Tc-HYNIC-(tricine)-(Ser) 3 -LTVPWY peptide exhibited overexpressed HER2 tumor targeting.

99m Tc-HYNIC-(Ser) 3 -LTVPWY peptide bearing tricine as co-ligand for targeting and imaging of HER2 overexpression tumor