Cytotoxicity Comparison of ^99mTc-Labeled Peptide Antagonist and Agonist Targeting the SSTR2 Receptor in AR42J Cells

Auger electrons are low-energy, high-linear-energy-transfer particles that deposit their energy over nanometers distances. Their biological impact depends heavily on where the radionuclide is localized within the cell. To verify the hypothesis that the cell membrane may be a better molecular target than the cytoplasm in Auger electron therapy, we investigated whether the radiotoxicity of ^99mTc varied depending on its location in the cell. The behavior of peptide radiopharmaceuticals ^99mTc-TECANT-1 targeted the cell membrane was compared with ^99mTc-TEKTROTYD directed to the cytoplasm. Our findings confirmed that ^99mTc-TECANT-1 displayed greater binding to AR-42-J cells than ^99mTc-TEKTROTYD. Additionally, it was demonstrated that the receptor agonist ^99mTc-TEKTROTYD is localized in more than 90% of the cytoplasm, while ^99mTc-TECANT-1 is found in 60-80% of the cell membrane. When evaluating cell survival using the MTS assay, we observed that toxicity was significantly higher when ^99mTc was targeted to the membrane compared to the cytoplasm. This indicates that, for ^99mTc, as with ¹⁶¹Tb, the membrane is a more sensitive target for Auger electrons than the cytoplasm. Our results also suggest that receptor antagonists labelled with therapeutic doses of ^99mTc may be effective in treating certain cancers. However, further detailed studies, particularly dosimetric investigations, are necessary to validate these findings.