ArticlePloS one2014
DNA double strand breaks as predictor of efficacy of the alpha-particle emitter Ac-225 and the electron emitter Lu-177 for somatostatin receptor targeted radiotherapy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 136 citations in OpenAlex.
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- Emerging role of radiopharmaceutical therapy in oncology: advances, challenges, and future directions.JNCI cancer spectrum · 2026Review
- Radiation Biology of Radiopharmaceuticals: Beyond External Beam Radiation Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Astatine-211-Towards In Vivo Stable Astatine-211 Labeled Radiopharmaceuticals and Their (Pre)Clinical Applications.Medicinal research reviews · 2026Review
- Radiopharmaceutical: An Update and Comparison of Preclinical Investigation Result of Alpha and Beta Emitter Radioisotope.Drug design, development and therapy · 2026Review
- Targeting Tumor-Infiltrating Immune Cells for Targeted Alpha Therapy in Gliomas: Optimization of [225Ac]Ac-DOTA-αCD11b Dosing through PET Imaging.Molecular cancer therapeutics · 2025Article
- Alpha Particle Emitter Radiolabeled Antibodies in Cancer Therapy: Current Status, Challenges, and Future Prospects.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Advances in PSMA-Targeted Radionuclide Therapeutics.Current treatment options in oncology · 2025Review
- Preclinical safety and effectiveness of a long-acting somatostatin analogue [European journal of nuclear medicine and molecular imaging · 2025Article
- Preclinical investigation of [European journal of nuclear medicine and molecular imaging · 2025Article
- Exploring the therapeutic potential of localized alpha irradiation for cancer: from DNA damage to immune activation.BJR open · 2025Review
- Comparison of ZnS(Ag) Scintillator and Proportional Counter Tube for Alpha Detection in Thin-Layer Chromatography.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Design ofAnnals of translational medicine · 2024Review
- Recent advances and impending challenges for the radiopharmaceutical sciences in oncology.The Lancet. Oncology · 2024Review
- Towards Effective Targeted Alpha Therapy for Neuroendocrine Tumours: A Review.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Structural modifications toward improved lead-203/lead-212 peptide-based image-guided alpha-particle radiopharmaceutical therapies for neuroendocrine tumors.European journal of nuclear medicine and molecular imaging · 2024Article
- Tumor targeted alpha particle therapy with an actinium-225 labelled antibody for carbonic anhydrase IX.Chemical science · 2024Article
- Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives.EJNMMI radiopharmacy and chemistry · 2024Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleKey biologic effects of the alpha-particle emitter Actinium-225 in comparison to the beta-particle emitter Lutetium-177 labeled somatostatin-analogue DOTATOC in vitro and in vivo were studied to evaluate the significance of γH2AX-foci formation.
methodsTo determine the relative biological effectiveness (RBE) between the two isotopes (as - biological consequence of different ionisation-densities along a particle-track), somatostatin expressing AR42J cells were incubated with Ac-225-DOTATOC and Lu-177-DOTATOC up to 48 h and viability was analyzed using the MTT assay. DNA double strand breaks (DSB) were quantified by immunofluorescence staining of γH2AX-foci. Cell cycle was analyzed by flow cytometry. In vivo uptake of both radiolabeled somatostatin-analogues into subcutaneously growing AR42J tumors and the number of cells displaying γH2AX-foci were measured. Therapeutic efficacy was assayed by monitoring tumor growth after treatment with activities estimated from in vitro cytotoxicity.
resultsAc-225-DOTATOC resulted in ED50 values of 14 kBq/ml after 48 h, whereas Lu-177-DOTATOC displayed ED50 values of 10 MBq/ml. The number of DSB grew with increasing concentration of Ac-225-DOTATOC and similarly with Lu-177-DOTATOC when applying a factor of 700-fold higher activity compared to Ac-225. Already 24 h after incubation with 2.5-10 kBq/ml, Ac-225-DOTATOC cell-cycle studies showed up to a 60% increase in the percentage of tumor cells in G2/M phase. After 72 h an apoptotic subG1 peak was also detectable. Tumor uptake for both radio peptides at 48 h was identical (7.5%ID/g), though the overall number of cells with γH2AX-foci was higher in tumors treated with 48 kBq Ac-225-DOTATOC compared to tumors treated with 30 MBq Lu-177-DOTATOC (35% vs. 21%). Tumors with a volume of 0.34 ml reached delayed exponential tumor growth after 25 days (44 kBq Ac-225-DOTATOC) and after 21 days (34 MBq Lu-177-DOTATOC).
conclusionγH2AX-foci formation, triggered by beta- and alpha-irradiation, is an early key parameter in predicting response to internal radiotherapy.
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