{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:55:29Z","timestamp":1790931329439,"version":"4.1.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1007\/s00259-026-08092-x","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:54:00Z","timestamp":1784775240000},"page":"7233-7247","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deciphering the phenotypic responses to 177Lu-based radioligand therapy to identify efficacious combinations"],"prefix":"10.1007","volume":"53","author":[{"given":"Marco","family":"Ranzani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Cicconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Sastre-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmita","family":"Thapa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefine","family":"Reber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Barlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Laure","family":"Boursier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Cerutti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Deberle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Del Pozzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Elinati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lerin","family":"Geo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Grinkevich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlene","family":"Hartnagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sravanth K.","family":"Hindupur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katjusa","family":"Koler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suraj","family":"Menon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Neves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Schacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eeson","family":"Rajendra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Reschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Schmelzle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme C. M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0414-0740","authenticated-orcid":false,"given":"Helen M. R.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Cortes-Cros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"8092_CR1","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41573-020-0073-9","volume":"19","author":"G Sgouros","year":"2020","unstructured":"Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov. 2020;19:589\u2013608. https:\/\/doi.org\/10.1038\/s41573-020-0073-9.","journal-title":"Nat Rev Drug Discov"},{"key":"8092_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-025-01069-z","author":"I Primac","year":"2025","unstructured":"Primac I, Tabury K, Tasdogan A, Baatout S, Herrmann K. The molecular blueprint of targeted radionuclide therapy. Nat Rev Clin Oncol. 2025. https:\/\/doi.org\/10.1038\/s41571-025-01069-z.","journal-title":"Nat Rev Clin Oncol"},{"key":"8092_CR3","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41420-023-01778-3","volume":"10","author":"T Zhang","year":"2024","unstructured":"Zhang T, Lei H, Chen X, Dou Z, Yu B, Su W, et al. Carrier systems of radiopharmaceuticals and the application in cancer therapy. Cell Death Discov. 2024;10:16. https:\/\/doi.org\/10.1038\/s41420-023-01778-3.","journal-title":"Cell Death Discov"},{"key":"8092_CR4","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1056\/NEJMoa1607427","volume":"376","author":"J Strosberg","year":"2017","unstructured":"Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 Trial of (177)Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017;376:125\u201335. https:\/\/doi.org\/10.1056\/NEJMoa1607427.","journal-title":"N Engl J Med"},{"key":"8092_CR5","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","volume":"385","author":"O Sartor","year":"2021","unstructured":"Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021;385:1091\u2013103. https:\/\/doi.org\/10.1056\/NEJMoa2107322.","journal-title":"N Engl J Med"},{"key":"8092_CR6","doi-asserted-by":"publisher","unstructured":"Jang A, Kendi AT, Johnson GB, Halfdanarson TR, Sartor O. Targeted alpha-particle therapy: A review of current trials. int J Mol Sci. 2023;24. https:\/\/doi.org\/10.3390\/ijms241411626.","DOI":"10.3390\/ijms241411626"},{"key":"8092_CR7","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/s0079-6603(08)60611-x","volume":"35","author":"JF Ward","year":"1988","unstructured":"Ward JF. DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability. Prog Nucleic Acid Res Mol Biol. 1988;35:95\u2013125. https:\/\/doi.org\/10.1016\/s0079-6603(08)60611-x.","journal-title":"Prog Nucleic Acid Res Mol Biol"},{"key":"8092_CR8","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1038\/nature08467","volume":"461","author":"SP Jackson","year":"2009","unstructured":"Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461:1071\u20138. https:\/\/doi.org\/10.1038\/nature08467.","journal-title":"Nature"},{"key":"8092_CR9","doi-asserted-by":"publisher","first-page":"362ps17","DOI":"10.1126\/scitranslmed.aaf9246","volume":"8","author":"Y Pommier","year":"2016","unstructured":"Pommier Y, O\u2019Connor MJ, de Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci Transl Med. 2016;8:362ps17. https:\/\/doi.org\/10.1126\/scitranslmed.aaf9246.","journal-title":"Sci Transl Med"},{"key":"8092_CR10","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.7150\/thno.15311","volume":"6","author":"J Nonnekens","year":"2016","unstructured":"Nonnekens J, van Kranenburg M, Beerens CEMT, Suker M, Doukas M, van Eijck CHJ, et al. Potentiation of Peptide Receptor Radionuclide Therapy by the PARP Inhibitor Olaparib. Theranostics. 2016;6:1821\u201332. https:\/\/doi.org\/10.7150\/thno.15311.","journal-title":"Theranostics"},{"key":"8092_CR11","doi-asserted-by":"publisher","first-page":"10196","DOI":"10.1038\/s41598-020-67199-9","volume":"10","author":"C Cullinane","year":"2020","unstructured":"Cullinane C, Waldeck K, Kirby L, Rogers BE, Eu P, Tothill RW, et al. Enhancing the anti-tumour activity of (177)Lu-DOTA-octreotate radionuclide therapy in somatostatin receptor-2 expressing tumour models by targeting PARP. Sci Rep-Uk. 2020;10:10196. https:\/\/doi.org\/10.1038\/s41598-020-67199-9.","journal-title":"Sci Rep-Uk"},{"key":"8092_CR12","doi-asserted-by":"publisher","first-page":"4099","DOI":"10.1007\/s00259-024-06844-1","volume":"51","author":"H Rauch","year":"2024","unstructured":"Rauch H, Kitzberger C, Janghu K, Hawarihewa P, Nguyen NT, Min Y, et al. Combining [(177)Lu]Lu-DOTA-TOC PRRT with PARP inhibitors to enhance treatment efficacy in small cell lung cancer. Eur J Nucl Med Mol Imaging. 2024;51:4099\u2013110. https:\/\/doi.org\/10.1007\/s00259-024-06844-1.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"8092_CR13","doi-asserted-by":"publisher","first-page":"707","DOI":"10.2967\/jnumed.124.268902","volume":"66","author":"A Hallqvist","year":"2025","unstructured":"Hallqvist A, Brynjarsdottir E, Krantz T, Sjogren M, Svensson J, Bernhardt P. (177)Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial. J Nucl Med. 2025;66:707\u201312. https:\/\/doi.org\/10.2967\/jnumed.124.268902.","journal-title":"J Nucl Med"},{"key":"8092_CR14","doi-asserted-by":"publisher","unstructured":"Feijtel D, Reuvers TGA, Serooskerken CV, de Ridder CMA, Stuurman DC, de Blois E, et al. In Vivo Efficacy Testing of Peptide Receptor Radionuclide Therapy Radiosensitization Using Olaparib. Cancers. 2023;15. https:\/\/doi.org\/10.3390\/cancers15030915.","DOI":"10.3390\/cancers15030915"},{"key":"8092_CR15","doi-asserted-by":"publisher","unstructured":"Ruigrok EAM, Verkaik NS, de Blois E, de Ridder C, Stuurman D, Roobol SJ, et al. Preclinical Assessment of the Combination of PSMA-Targeting Radionuclide Therapy with PARP Inhibitors for Prostate Cancer Treatment. Int J Mol Sci. 2022;23. https:\/\/doi.org\/10.3390\/ijms23148037.","DOI":"10.3390\/ijms23148037"},{"key":"8092_CR16","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/s41580-019-0152-0","volume":"20","author":"R Scully","year":"2019","unstructured":"Scully R, Panday A, Elango R, Willis NA. DNA double-strand break repair-pathway choice in somatic mammalian cells. Nat Rev Mol Cell Biol. 2019;20:698\u2013714. https:\/\/doi.org\/10.1038\/s41580-019-0152-0.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"8092_CR17","doi-asserted-by":"publisher","first-page":"4745","DOI":"10.7150\/thno.84628","volume":"13","author":"K Waldeck","year":"2023","unstructured":"Waldeck K, Van Zuylekom J, Cullinane C, Gulati T, Simpson KJ, Tothill RW, et al. A genome-wide CRISPR\/Cas9 screen identifies DNA-PK as a sensitiser to 177Lutetium-DOTA-octreotate radionuclide therapy. Theranostics. 2023;13:4745\u201361. https:\/\/doi.org\/10.7150\/thno.84628.","journal-title":"Theranostics"},{"key":"8092_CR18","doi-asserted-by":"publisher","first-page":"3117","DOI":"10.7150\/thno.82963","volume":"13","author":"TGA Reuvers","year":"2023","unstructured":"Reuvers TGA, Verkaik NS, Stuurman D, de Ridder C, Groningen MCC, de Blois E, et al. DNA-PKcs inhibitors sensitize neuroendocrine tumor cells to peptide receptor radionuclide therapy in vitro and in vivo. Theranostics. 2023;13:3117\u201330. https:\/\/doi.org\/10.7150\/thno.82963.","journal-title":"Theranostics"},{"key":"8092_CR19","doi-asserted-by":"publisher","first-page":"385","DOI":"10.2967\/jnumed.124.268695","volume":"66","author":"CN Johnstone","year":"2025","unstructured":"Johnstone CN, Osellame LD, Cao Z, McDonald AF, Rigopoulos A, Burvenich IJG, et al. DNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of (177)Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma. J Nucl Med. 2025;66:385\u201390. https:\/\/doi.org\/10.2967\/jnumed.124.268695.","journal-title":"J Nucl Med"},{"key":"8092_CR20","doi-asserted-by":"publisher","first-page":"12723","DOI":"10.1021\/acs.jmedchem.1c00762","volume":"64","author":"M Berger","year":"2021","unstructured":"Berger M, Wortmann L, Buchgraber P, Lucking U, Zitzmann-Kolbe S, Wengner AM, et al. BAY-8400: A Novel Potent and Selective DNA-PK Inhibitor which Shows Synergistic Efficacy in Combination with Targeted Alpha Therapies. J Med Chem. 2021;64:12723\u201337. https:\/\/doi.org\/10.1021\/acs.jmedchem.1c00762.","journal-title":"J Med Chem"},{"key":"8092_CR21","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.2967\/jnumed.123.265433","volume":"64","author":"C Meyer","year":"2023","unstructured":"Meyer C, Stuparu A, Lueckerath K, Calais J, Czernin J, Slavik R, et al. Tandem Isotope Therapy with225Ac- and177Lu-PSMA-617 in a Murine Model of Prostate Cancer. J Nucl Med. 2023;64:1772\u20138. https:\/\/doi.org\/10.2967\/jnumed.123.265433.","journal-title":"J Nucl Med"},{"key":"8092_CR22","doi-asserted-by":"publisher","unstructured":"Khazaei Monfared Y, Heidari P, Klempner SJ, Mahmood U, Parikh AR, Hong TS, et al. DNA Damage by radiopharmaceuticals and mechanisms of cellular repair. Pharmaceutics. 2023;15. https:\/\/doi.org\/10.3390\/pharmaceutics15122761.","DOI":"10.3390\/pharmaceutics15122761"},{"key":"8092_CR23","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1089\/ars.2013.5489","volume":"21","author":"JA Reisz","year":"2014","unstructured":"Reisz JA, Bansal N, Qian J, Zhao WL, Furdui CM. Effects of Ionizing Radiation on Biological Molecules-Mechanisms of Damage and Emerging Methods of Detection. Antioxid Redox Sign. 2014;21:260\u201392. https:\/\/doi.org\/10.1089\/ars.2013.5489.","journal-title":"Antioxid Redox Sign"},{"key":"8092_CR24","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/1748-717X-6-64","volume":"6","author":"NA Franken","year":"2011","unstructured":"Franken NA, ten Cate R, Krawczyk PM, Stap J, Haveman J, Aten J, et al. Comparison of RBE values of high-LET alpha-particles for the induction of DNA-DSBs, chromosome aberrations and cell reproductive death. Radiat Oncol. 2011;6:64. https:\/\/doi.org\/10.1186\/1748-717X-6-64.","journal-title":"Radiat Oncol"},{"key":"8092_CR25","doi-asserted-by":"publisher","first-page":"418","DOI":"10.2174\/138920212802510501","volume":"13","author":"TE Schmid","year":"2012","unstructured":"Schmid TE, Zlobinskaya O, Multhoff G. Differences in Phosphorylated Histone H2AX Foci Formation and Removal of Cells Exposed to Low and High Linear Energy Transfer Radiation. Curr Genomics. 2012;13:418\u201325. https:\/\/doi.org\/10.2174\/138920212802510501.","journal-title":"Curr Genomics"},{"key":"8092_CR26","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1016\/j.ijrobp.2017.11.012","volume":"100","author":"RJ Carter","year":"2018","unstructured":"Carter RJ, Nickson CM, Thompson JM, Kacperek A, Hill MA, Parsons JL. Complex DNA Damage Induced by High Linear Energy Transfer Alpha-Particles and Protons Triggers a Specific Cellular DNA Damage Response. Int J Radiat Oncol. 2018;100:776\u201384. https:\/\/doi.org\/10.1016\/j.ijrobp.2017.11.012.","journal-title":"Int J Radiat Oncol"},{"key":"8092_CR27","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1146\/annurev-biochem-080320-110356","volume":"90","author":"BM Stinson","year":"2021","unstructured":"Stinson BM, Loparo JJ. Repair of DNA Double-Strand Breaks by the Nonhomologous End Joining Pathway. Annu Rev Biochem. 2021;90:137\u201364. https:\/\/doi.org\/10.1146\/annurev-biochem-080320-110356.","journal-title":"Annu Rev Biochem"},{"key":"8092_CR28","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.cell.2020.05.040","volume":"182","author":"M Olivieri","year":"2020","unstructured":"Olivieri M, Cho T, Alvarez-Quil\u00f3n A, Li KJ, Schellenberg MJ, Zimmermann M, et al. A Genetic Map of the Response to DNA Damage in Human Cells. Cell. 2020;182:481\u2013. https:\/\/doi.org\/10.1016\/j.cell.2020.05.040.","journal-title":"Cell"},{"key":"8092_CR29","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/s41580-021-00394-2","volume":"22","author":"JH Lee","year":"2021","unstructured":"Lee JH, Paull TT. Cellular functions of the protein kinase ATM and their relevance to human disease. Nat Rev Mol Cell Biol. 2021;22:796\u2013814. https:\/\/doi.org\/10.1038\/s41580-021-00394-2.","journal-title":"Nat Rev Mol Cell Biol"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-08092-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-026-08092-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-08092-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:31:51Z","timestamp":1790929911000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-026-08092-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":29,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["8092"],"URL":"https:\/\/doi.org\/10.1007\/s00259-026-08092-x","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"assertion":[{"value":"20 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Xenograft studies were performed at Novartis, approved by the Cantonal Veterinary Office of Basel Stadt, Switzerland, and in strict adherence to the Swiss Federal Animal Welfare Act and Ordinance.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Al.Ci, A.T., E.E., L.G., V.G., S.M., J.N., G.C.M.S. and H.M.R.R. are all employees and shareholders of Artios Pharma Ltd. Ma.Ra., J.B., M.L.B., Au.Ce., K.K., N.S. and E.R. are former employees and shareholders of Artios Pharma Ltd. S.M. and G.C.M.S. are shareholders of AstraZeneca PLC. H.M.R.R. is a shareholder of Mission Therapeutics. A.T. has share options with Benevolent AI. Ma.Ra., E.R., G.C.M.S. and H.M.R.R. hold patents with Artios Pharma Ltd. G.C.M.S. also reports a patent with AstraZeneca PLC. H.M.R.R. also reports a patent with Mission Therapeutics. G.S.-M., E.S., J.R., L.D., L.D.P., C.H., S.K.H., B.S., Ma.Re., T.S. and M.C.-C. are employees of Novartis Pharma and hold stock in Novartis. T.S., Ma.Re., J.R., S.K.H., and M.C.-C. also report a patent with Novartis Pharma AG.","order":2,"name":"Ethics","label":"Competing interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}