An improved Tc-99m-HYNIC-(Ser)(3)-LTVSPWY peptide with EDDA/tricine as co-ligands for targeting and imaging of HER2 overexpression tumor

作者：Khodadust Fatemeh; Ahmadpour Sajjad; Aligholikhamseh Nazan; Abedi Seyed Mohammad; Hosseinimehr Seyed Jalal

来源：European Journal of Medicinal Chemistry, 2018, 144: 767-773.

DOI：10.1016/j.ejmech.2017.12.037

• HER2
• Imaging
• LTVSPWY
• HYNIC
• Tumor
• EDDA

Overexpression of human epidermal receptor 2 (HER2) has given the opportunity for targeting and delivering of imaging radiotracers. The aim of this study was to evaluate the Tc-99m-HYNIC-(EDDA/tricine)-(Ser)(3)-LTVSPWY peptide for tumor targeting and imaging of tumor with overexpression of HER2. The HYNIC-(Ser)(3)-LTVSPWY was labeled with Tc-99m in presence of EDDA/tricine mixture as co-ligands. The in vitro and in vivo studies of this radiolabeled peptide were performed for cellular specific binding and tumor targeting. The high radiochemical purity of Tc-99m-HYNIC (EDDA/tricine)-(Ser)(3)-LTVSPWY was obtained to be 99%. It exhibited high stability in normal saline and human serum. In HER2 binding affinity study, a significant reduction in uptake of radiolabeled peptide (7.7 fold) was observed by blocking SKOV-3 cells receptors with unlabeled peptide. The K-D and B-max values for this radiolabeled peptide were determined as 33 +/- 1.0 nM and 2.9 +/- 0.3 x 10(6) CPM/pMol, respectively. Biodistribution study revealed tumor to blood and tumor to muscle ratios about 6.9 and 4 respectively after 4 h. Tumor imaging by gamma camera demonstrated considerable high contrast tumor uptake. This developed 99mTc-HYNIC-(Ser)3-LTVSPWY peptide selectively targeted on HER2 tumor and exhibited a high target uptake combined with acceptable low background activity for tumor imaging in mice. The results of this study and its comparison with another study showed that Tc-99m-HYNIC-(EDDA/tricine)-(Ser)(3)-LTVSPWY is much better than previously reported radiolabeled peptide as Tc-99m-CSSS-LTVSPWY for HER2 over expression tumor targeting and imaging.

• 出版日期2018-1-20