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Gastric cancer (GC) is still ranked fourth among malignant cancers and remained as the second leading cause of cancer related death. There is mounting evidence that emphasizes on the need for further investigation on the specific receptors overexpression roles in GC progression. Low efficiency and impotence of the common methods for targeting gastric tumorigenesis and related metastases are enough to convince researchers to continue their investigation on new approaches of effective GC targeting. Due to the suitable characteristics of peptides, such as high affinity and specificity, they have great potential for cancer cell targeting. Overexpression of specific targets in GC can facilitate the application of peptide-based pharmaceuticals for effective tumor targeting and therapy and early diagnosis with help of fluorescents or radionuclides. In this review article, we paid particular attention to the characterization of peptide-based pharmaceuticals and radiopharmaceuticals that have been investigated in recent years for GC diagnosis and therapy.

So far, numerous molecules and biomolecules have been evaluated for tumor targeting purposes for radionuclide-based imaging and therapy modalities. Due to the high affinity and specificity against tumor antigens, monoclonal antibodies are appropriate candidates for tumor targeting. However, their large size prevents their comprehensive application in radionuclide-based tumor imaging or therapy, since it leads to their low tumor penetration, low blood clearance, and thus inappropriate tumor-to-background ratio. Nowadays, the variable domain of heavy-chain antibodies from the Camelidae family, known as nanobodies (Nbs), turn into exciting candidates for medical research. Considering several innate advantages of these new tumor-targeting agents, including excellent affinity and specificity toward antigen, high solubility, high stability, fast washout from blood, convenient production, ease of selection, and low immunogenicity, it assumes that they may overcome generic problems of monoclonal antibodies, their fragments, and other vectors used for tumor imaging/therapy. After three decades of Nbs discovery, the increasing number of their preclinical and clinical investigations, which have led to outstanding results, confirm their application for tumor targeting purposes. This review describes Nbs characteristics, the diagnostic and therapeutic application of their radioconjugates, and their recent advances.

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 99mTc-HYNIC-(tricine)-(Ser)3-LTVPWY peptide for tumor targeting and imaging with overexpression of HER2. HYNIC-(Ser)3-LTVPWY peptide was labeled with 99mTc 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 99mTc-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 99mTc 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 KD and Bmax values were found 2.6±0.5 nM and (2.6±0.1)×106, 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. 99mTc-HYNIC-(tricine)-(Ser)3-LTVPWY peptide exhibited overexpressed HER2 tumor targeting.

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 99mTc-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 99mTc 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 99mTc-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 KD and Bmax values for this radiolabeled peptide were determined as 3.3 ± 1.0 nM and 2.9 ± 0.3 × 106 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 99mTc-HYNIC-(EDDA/tricine)-(Ser)3-LTVSPWY is much better than previously reported radiolabeled peptide as 99mTc-CSSS-LTVSPWY for HER2 overexpression tumor targeting and imaging.

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