ArticleAntioxidants & redox signaling2016
Localized Irradiation of Cell Membrane by Auger Electrons Is Cytotoxic Through Oxidative Stress-Mediated Nontargeted Effects.
Article in Antioxidants & redox signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 90 citations in OpenAlex.
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- Comparative theranostic efficacy ofEuropean journal of nuclear medicine and molecular imaging · 2026Article
- Ion Beam Imaging Shows Selective Thallium-201 Uptake in Cell Nuclei: Impact on Cellular Dosimetry and Radiotoxicity of Auger Electron Emitters.Chemical & biomedical imaging · 2026Article
- Radiation Biology of Radiopharmaceuticals: Beyond External Beam Radiation Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Cellular responses to targeted radionuclide therapy: rethinking radiobiology under continuous low dose rates.Frontiers in oncology · 2026Review
- Targeted alpha therapy: a comprehensive analysis of the biological effects from "local-regional-systemic" dimensions.European journal of nuclear medicine and molecular imaging · 2025Review
- Monte Carlo-based subcellular comparison of electron energy deposition byEJNMMI physics · 2025Article
- Coordination Chemistry of Emerging Meitner-Auger Electron-Emitting Radiometals for Targeted Radionuclide Therapy.Coordination chemistry reviews · 2025Article
- The molecular blueprint of targeted radionuclide therapy.Nature reviews. Clinical oncology · 2025Review
- MHC-I-Driven Antitumor Immunity Counterbalances Low Absorbed Doses of Radiopharmaceutical Therapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Cytotoxicity Comparison ofMolecules (Basel, Switzerland) · 2025Article
- Extracellular vesicles role in radio(nuclide)therapy.Journal of radiation research · 2024Review
- In Vitro and Preclinical Systematic Dose-Effect Studies of Auger Electron- and β Particle-Emitting Radionuclides and External Beam Radiation for Cancer Treatment.International journal of radiation oncology, biology, physics · 2024Article
- Terbium radionuclides for theranostic applications in nuclear medicine: from atom to bedside.Theranostics · 2024Review
- Palladium-103 (Theranostics · 2024Article
- DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair.Pharmaceutics · 2023Review
- Alpha Particle-Emitting Radiopharmaceuticals as Cancer Therapy: Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery.Molecular imaging and biology · 2023Review
- Radiopharmaceuticals as combinatorial partners for immune checkpoint inhibitors.Trends in cancer · 2023Review
- Au@EJNMMI radiopharmacy and chemistry · 2023Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsWe investigated whether radiation-induced nontargeted effects are involved in the cytotoxic effects of anticell surface monoclonal antibodies labeled with Auger electron emitters, such as iodine 125 (monoclonal antibodies labeled with (125)I [(125)I-mAbs]).
resultsWe showed that the cytotoxicity of (125)I-mAbs targeting the cell membrane of p53(+/+) HCT116 colon cancer cells is mainly due to nontargeted effects. Targeted and nontargeted cytotoxicities were inhibited in vitro following lipid raft disruption with Methyl-β-cyclodextrin (MBCD) or filipin or use of radical oxygen species scavengers. (125)I-mAb efficacy was associated with acid sphingomyelinase activation and modulated through activation of the AKT, extracellular signal-related kinase ½ (ERK1/2), p38 kinase, c-Jun N-terminal kinase (JNK) signaling pathways, and also of phospholipase C-γ (PLC-γ), proline-rich tyrosine kinase 2 (PYK-2), and paxillin, involved in Ca(2+) fluxes. Moreover, the nontargeted response induced by directing 5-[(125)I]iodo-2'-deoxyuridine to the nucleus was comparable to that of (125)I-mAb against cell surface receptors. In vivo, we found that the statistical significance of tumor growth delay induced by (125)I-mAb was removed after MBCD treatment and observed oxidative DNA damage beyond the expected Auger electron range. These results suggest the involvement of nontargeted effects in vivo also. INNOVATION: Low-energy Auger electrons, such as those emitted by (125)I, have a short tissue range and are usually targeted to the nucleus to maximize their cytotoxicity. In this study, we show that targeting the cancer cell surface with (125)I-mAbs produces a lipid raft-mediated nontargeted response that compensates for the inferior efficacy of non-nuclear targeting.
conclusionOur findings describe the mechanisms involved in the efficacy of (125)I-mAbs targeting the cancer cell surface. Antioxid. Redox Signal. 25, 467-484.
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