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

## TL;DR

This study compares the cytotoxic effects of two 99mTc-labeled peptides targeting different cell locations and finds that targeting the cell membrane is more effective.

## Contribution

The study demonstrates that 99mTc radiotoxicity is higher when localized to the cell membrane versus the cytoplasm.

## Key findings

- 99mTc-TECANT-1 showed greater binding to AR-42-J cells than 99mTc-TEKTROTYD.
- 99mTc-TEKTROTYD localized to over 90% cytoplasm, while 99mTc-TECANT-1 was in 60–80% cell membrane.
- Membrane-targeted 99mTc caused significantly higher toxicity than cytoplasm-targeted 99mTc.

## Abstract

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.