Nosrati Shanjani Sahar, Łyczko Monika, Walczak Rafał, Koźmiński Przemysław, Majka Emilia, Narbutt Jerzy, Wojdowska Wioletta, Majkowska-Pilip Agnieszka, Bilewicz Aleksander
Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
National Centre for Nuclear Research, Sołtana 7/3, 05-400 Otwock, Poland.
Molecules. 2025 Apr 11;30(8):1715. doi: 10.3390/molecules30081715.
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 Tc varied depending on its location in the cell. The behavior of peptide radiopharmaceuticals Tc-TECANT-1 targeted the cell membrane was compared with Tc-TEKTROTYD directed to the cytoplasm. Our findings confirmed that Tc-TECANT-1 displayed greater binding to AR-42-J cells than Tc-TEKTROTYD. Additionally, it was demonstrated that the receptor agonist Tc-TEKTROTYD is localized in more than 90% of the cytoplasm, while Tc-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 Tc was targeted to the membrane compared to the cytoplasm. This indicates that, for Tc, as with Tb, 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 Tc may be effective in treating certain cancers. However, further detailed studies, particularly dosimetric investigations, are necessary to validate these findings.
俄歇电子是低能量、高线性能量传递的粒子，它们在纳米距离内沉积能量。它们对生物的影响在很大程度上取决于放射性核素在细胞内的定位。为了验证在俄歇电子治疗中细胞膜可能比细胞质是更好的分子靶点这一假设，我们研究了锝的放射毒性是否因其在细胞中的位置而异。将靶向细胞膜的肽放射性药物锝 - TECANT - 1的行为与导向细胞质的锝 - TEKTROTYD进行了比较。我们的研究结果证实，锝 - TECANT - 1与AR - 42 - J细胞的结合比锝 - TEKTROTYD更强。此外，已证明受体激动剂锝 - TEKTROTYD有超过90%定位于细胞质中，而锝 - TECANT - 1有60 - 80%存在于细胞膜中。当使用MTS法评估细胞存活情况时，我们观察到与细胞质相比，当锝靶向细胞膜时毒性显著更高。这表明，对于锝来说，与铽一样，细胞膜对俄歇电子是比细胞质更敏感的靶点。我们的结果还表明，用治疗剂量的锝标记的受体拮抗剂可能对治疗某些癌症有效。然而，需要进一步详细的研究，特别是剂量学研究，来验证这些发现。
