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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.
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RATIONALE: Key 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. METHODS: To 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. RESULTS: Ac-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). CONCLUSION: γH2AX-foci formation, triggered by beta- and alpha-irradiation, is an early key parameter in predicting response to internal radiotherapy.
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“225Ac and 177Lu triggered-γH2AX-foci formation is an early key parameter in predicting response to internal radiotherapy.”
From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [156]
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Cites
Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing
Tice, R. R., Agurell, E., Anderson, D. C., Burlinson, B., Hartmann, A., Kobayashi, H., Miyamae, Y., Rojas, E., Ryu, J., & Sasaki, Y. F. (2000) · Environmental and Molecular Mutagenesis · doi:10.1002/(sici)1098-2280(2000)35:3 · Cited by 4,885
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466
The comet assay: a method to measure DNA damage in individual cells
Olive, P. L., & Banáth, J. P. (2006) · Nature Protocols · doi:10.1038/nprot.2006.5 · Cited by 1,845
-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin
Kinner, A., Wu, W., Staudt, C., & Iliakis, G. E. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn550 · Cited by 1,303
Peptide Receptors as Molecular Targets for Cancer Diagnosis and Therapy
Reubi, J. C. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0007 · Cited by 1,144
Olive, P. L., Banáth, J. P., Durand, R. E., & Banáth, J. P. (1990) · Radiation Research · doi:10.2307/3577587 · Cited by 1,095
Olive, P. L., Banáth, J. P., & Durand, R. E. (2012) · Radiation Research · doi:10.1667/rrav04.1 · Cited by 1,031
Sgouros, G., Roeske, J. C., McDevitt, M. R., Palm, S., Allen, B. J., Fisher, D. R., Brill, A. B., Song, H., Howell, R. W., & Akabani, G. (2010) · Journal of Nuclear Medicine · doi:10.2967/jnumed.108.058651 · Cited by 552
Tumor therapy with targeted atomic nanogenerators.
McDevitt, M. R., Ma, D., Lai, L. T., Simon, J., Borchardt, P., Frank, R. K., Wu, K., Pellegrini, V., Curcio, M. J., Miederer, M., et al. (2001) · Science · doi:10.1126/science.1064126 · Cited by 501
Self-citationRadioimmunotherapy with alpha-emitting nuclides
McDevitt, M. R., Sgouros, G., Finn, R. D., Humm, J. L., Jurcic, J. G., Larson, S. M., & Scheinberg, D. A. (1998) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s002590050306 · Cited by 403
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Luhung, A., Hasanah, A. N., & Ramdhani, D. (2026) · Drug Design Development and Therapy · doi:10.2147/dddt.s570831 · Cited by 5
Carlsson, M. J., & Fahrer, J. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2788-4_16 · Cited by 5
Self-citationThe application of radionuclide therapy for breast cancer
Musket, A., Davern, S. M., Elam, B. M., Musich, P. R., Moorman, J. P., & Jiang, Y. (2024) · Frontiers in Nuclear Medicine · doi:10.3389/fnume.2023.1323514 · Cited by 5
Alpha-emitter Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors
Bhimaniya, S., Shah, H., & Jacene, H. A. (2024) · PET Clinics · doi:10.1016/j.cpet.2024.03.005 · Cited by 5
Jalalvand, Z., Zobdeh, P., & Sani, V. E. (2024) · Radiation Physics and Chemistry · doi:10.1016/j.radphyschem.2024.111670 · Cited by 5
Radiation Biology of Radiopharmaceuticals: Beyond External Beam Radiation Therapy
Olson, A. P., Engle, J. W., & Pandey, M. K. (2026) · Pharmaceuticals · doi:10.3390/ph19040591 · Cited by 4
Ordas, L., Foster, S., Pham, P., Ollendorff, A. S., Gnanasekar, V., Toulany, M., & Sodji, Q. H. (2026) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkag056 · Cited by 4
Gastro-Enteric-Pancreatic Neuroendocrine Tumor Treatment
Satapathy, S., Chandekar, K. R., & Bal, C. S. (2023) · PET Clinics · doi:10.1016/j.cpet.2022.11.004 · Cited by 4
Levy, O., Altaras, A., Binyamini, L., Sagi‐Assif, O., Izraely, S., Cooks, T., Kobiler, O., Gerlic, M., Kelson, I., Witz, I. P., et al. (2024) · Cancers · doi:10.3390/cancers16223804 · Cited by 4
Al-Ezzi, E. M., Abdeljalil, O., Lajkosz, K., Gramolini, S. S., Alqaisi, H. A., Peng, J., O’Dwyer, R., Alghamdi, M., Almuthri, S. A., Kumar, V., et al. (2025) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2025.06.004 · Cited by 4
Jaswal, A. P., Josefsson, A., Cortez, A. G., Bhise, A., Li, B., Sneiderman, C. T., Vincze, S. R., Nisnboym, M., Latoche, J. D., Day, K. E., et al. (2025) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-24-0996 · Cited by 3
Radiopharmaceuticals for molecular imaging and theranostics of glioblastoma
Pinto, C. I. G., Guerreiro, J. F., Silva, F., Mendes, F., & Paulo, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99873-4.00023-2 · Cited by 3
Satterlee, A., Attayek, P. J., Midkiff, B. R., & Huang, L. (2017) · Radiation Oncology · doi:10.1186/s13014-017-0794-z · Cited by 3
Bergholz, L. M., Grimminger, P., Dikeoulia, E., Rossmann, H., Weinmann, A., Moehler, M. H., Zimmermann, T., Weber, M. M., Galle, P. R., Kaina, B., et al. (2020) · Journal of Gastrointestinal and Liver Diseases · doi:10.15403/jgld-2589 · Cited by 3
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Emerging evidence for sequencing and combining PSMA-based therapies in prostate cancer
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Baum, R. P., Zhao, T., Jakobsson, V., Greifenstein, L., Eismant, A., Ghai, K., Mishra, A., Klega, A., Landvogt, C., Mueller, C., et al. (2026) · Journal of Nuclear Medicine · doi:10.2967/jnumed.125.271129 · Cited by 2
Aranda‐Lara, L., Trujillo-Nolasco, M., López-Marmolejo, C. M., Cárdenas-Rodríguez, K., Gómez-Pulido, V. O., Morales-Ávila, E., Ocampo‐García, B., Jiménez‐Mancilla, N., Estrada, J. A., Otero, G., et al. (2024) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2024.106274 · Cited by 2
Ilyas, A. M., Alam, M. K., Musah, J., Yang, M., Roy, V. A. L., Lam, Y. W., & Lau, C. (2021) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2021.113142 · Cited by 2
Pijeira, M. S. O., Gomes-da-Silva, N. C., Ricci‐Júnior, E., Alencar, L. M. R., İlem‐Özdemir, D., Cavalcanti, A. D. S., Machado, D. E., Perini, J. A., & Santos‐Oliveira, R. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123765 · Cited by 2
Evaluation of Rare Earths viewed from the Occupational Health
Shin, S., Rim, K.-T., & Kim, J.-C. (2016) · Journal of Korean Society of Occupational and Environmental Hygiene · doi:10.15269/jksoeh.2016.26.3.237 · Cited by 2
Chuvilin, D., Коков, К. В., Egorova, B. V., Makoveeva, K. A., Perminov, Y., & Прошин, М. А. (2019) · AIP conference proceedings · doi:10.1063/1.5099613 · Cited by 2
Alpha Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors
Beydağı, G., Selçuk, N. A., & Kabasakal, L. (2023) · Nuclear Medicine Seminars · doi:10.4274/nts.galenos.2023.0015 · Cited by 1
Hazout, S., Zwahlen, D. R., Oehler, C., Champion, A., Benzaquen, D., & Taussky, D. (2024) · BJR|Open · doi:10.1093/bjro/tzaf030 · Cited by 1
Коков, К. В., Demchenko, A. G., Egorova, B. V., Ларкин, А. А., Lyundup, A. V., Makoveeva, K. A., Moiseeva, A. N., Panchenko, V. Y., Прошин, М. А., Reshetov, I. V., et al. (2020) · Journal of Surface Investigation X-ray Synchrotron and Neutron Techniques · doi:10.1134/s102745102007023x · Cited by 1
Mason, C. A., Carter, L. M., & Lewis, J. S. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788016452-00271
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Reischl, G. (2019) · MDPI eBooks · doi:10.3390/books978-3-03921-314-6
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(2016) · Pan Stanford Publishing eBooks · doi:10.1201/9781315364735-2
Deblonde, G. J. ‐., Mattocks, J. A., Dong, Z., Wooddy, P. T., Cotruvo, J. A., & Zavarin, M. (2021) · ChemRxiv · doi:10.26434/chemrxiv.14763426
Wang, Y., Du, C., Gao, H., Kong, X., Xue, H., Zhang, W., Yin, Y., Wu, T., Yu, Y., Tu, Y., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2939649/v1
Peptide Receptor Radionuclide Therapy (PRRT)
Bozkurt, M. F. (2024) · Springer eBooks · doi:10.1007/978-3-031-56968-5_28
Clinical Experience in 225Ac-PSMA
Kairemo, K. (2025) · Springer eBooks · doi:10.1007/978-3-031-90337-3_15
Koniar, H., & Schaffer, P. C. (2025) · Royal Society of Chemistry eBooks · doi:10.1039/9781837677139-00056
Glypican-3 (GPC3) Targeted Radiopharmaceuticals for Treatment of Liver Cancer
He, R., Mezo, A. R., & Chen, G. (2025) · Royal Society of Chemistry eBooks · doi:10.1039/9781837677139-00202
Plan for the Neutron Irradiation Experimental Instruments
Inagaki, M., & Takamiya, K. (2025) · RADIOISOTOPES · doi:10.3769/radioisotopes.740214
Hasim, S. K. L., Castillo, M. C. M., Andig, R. J. T., Pasagui, J. R. M., & Velasco, J. L. (2026) · International journal of research and scientific innovation · doi:10.51244/ijrsi.2026.13020055
Impact de la radiothérapie interne vectorisée alpha sur le microenvironnement tumoral
Perrin, J. (2021) · theses.fr (ABES) · doi:10.70675/31c91866z101fz4e07zbde2z6887a8fdba6d
Araszkiewicz, M., Tymińska, K., Kaźmierczak, U., Chuchała, P., Grzyb, J., Kamińska, P., Kwiatkowski, R., Maleszewska, M., Malinowska, A., Maliszewska‐Olejniczak, K., et al. (2026) · Medical Physics · doi:10.1002/mp.70611
ImmunoPET-guided, antigen-stratified CAR T-cell therapy for neuroblastoma
Chung, J. H., Lee, J. M., & Hong, C. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.07.054
Winter, R., Bauder‐Wüst, U., Schäfer, M., Remde, Y., Roscher, M., Pérez, R. L., & Benešová, M. (2026) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2026.08.036
Metadata
- Authors
- Graf, F., Fahrer, J., Maus, S., Morgenstern, A., Bruchertseifer, F., Venkatachalam, S., Fottner, C., Weber, M. M., Huelsenbeck, J., Schreckenberger, M., Kaina, B., & Miederer, M.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- European Commission (BE)
- Corresponding author
- Miederer, Matthias
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-02-07
- Volume
- 9
- Issue
- 2
- Pages
- e88239
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3917860
- OpenAlex
- W1984398166
- Cited by
- 143
- References
- 33
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 18 · 2023: 19 · 2022: 12 · 2021: 17 · 2020: 12 · 2019: 16 · 2018: 15 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 1
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Gutenberg Open Science (submittedVersion, cc-by-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Joint Research Centre (European Commission) (submittedVersion)
- Gutenberg Open Science (cc-by)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Physical Sciences › Physics and Astronomy › Radiation › Radiation Therapy and Dosimetry
- Keywords
- actinium-225, lutetium-177, somatostatin receptors, targeted radiotherapy, alpha-emitting radionuclides, DNA double-strand breaks, γH2AX foci, relative biological effectiveness, DOTATOC, AR42J cells, tumor cell cycle, apoptosis, tumor uptake, treatment efficacy, somatostatin analogues
- MeSH terms
- Actinium, Alpha Particles, Animals, Cell Cycle, Lutetium, Radioisotopes, Cell Death, Receptors, Somatostatin, Neuroendocrine Tumors, Cell Line, Tumor, Rats, DNA Breaks, Double-Stranded
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