Abstract
Positron emission tomography (PET) with 68Ga-labeled peptides is a promising option in the imaging of tumors expressing peptide-binding receptors. PET scanning is non-invasive but involves internal exposure to ionizing radiation which could subsequently generate biological effects, particularly on targeted cells. The aim of the present study was to investigate the potential biological effects of 68Ga-labeled peptides on different targeted tumor cells in vitro. Human U87MG and HT-29 cells and murine AR42J and B16F10 cells were incubated with the following 68Ga-labeled peptides: 68Ga-NODAGA-c(RGDfK), 68Ga-DOTA-c(RGDfK), 68Ga-NOTA-TATE, 68Ga-DOTA-NOC, 68Ga-NODAGA-NOC, or 68Ga-NOTA-(Cys-39)-Exendin-4. Cell cycle analysis and annexin V/PI assay for apoptosis were performed by flow cytometry. Oxidative stress was evaluated by spectrophotometric measuring the level of reactive oxygen species (ROS) and total thiols. After incubation with 37 kBq/ml (1 µCi/ml) 68Ga-labeled peptides, generally observed an increase of apoptosis and cell cycle arrest, especially in G2/M. Furthermore, the increased ROS generation was mostly correlated with apoptosis. Our data demonstrated the ability of 68Ga-labeled peptides to exert significant inhibitory effects on tumor cell lines, through the cycle dysregulation and induction of apoptosis.
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