{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T16:35:00Z","timestamp":1780677300365,"version":"3.54.1"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Association Jules Bordet","award":["2021-27"],"award-info":[{"award-number":["2021-27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Peptide receptor radionuclide therapy with 177Lu-DOTATATE improves the outcome of patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Nevertheless, stable disease has been the main response pattern observed, with some rare complete responses. Lu-177 exerts about two-thirds of its biological effects via the indirect effects of ionizing radiation that generate reactive oxygen species, eventually leading to oxidative damage and cell death. This provides a rationale for targeting the antioxidant defence system in combination with 177Lu-DOTATATE. In the present study, the radiosensitizing potential and the safety of depleting glutathione (GSH) levels using buthionine sulfoximine (BSO) during 177Lu-DOTATATE therapy were assessed in vitro and in vivo using a xenograft mouse model. In vitro, the combination resulted in a synergistic effect in cell lines exhibiting a BSO-mediated GSH decrease. In vivo, BSO neither influenced 177Lu-DOTATATE biodistribution nor induced liver, kidney or bone marrow toxicity. In terms of efficacy, the combination resulted in reduced tumour growth and metabolic activity. Our results showed that disturbing the cell redox balance using a GSH synthesis inhibitor increased 177Lu-DOTATATE efficacy without additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with 177Lu-DOTATATE.<\/jats:p>","DOI":"10.3390\/cancers15082332","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T04:45:32Z","timestamp":1681706732000},"page":"2332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Disturbing the Redox Balance Using Buthionine Sulfoximine Radiosensitized Somatostatin Receptor-2 Expressing Pre-Clinical Models to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE"],"prefix":"10.3390","volume":"15","author":[{"given":"Wendy","family":"Delbart","sequence":"first","affiliation":[{"name":"Nuclear Medicine Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"},{"name":"Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwenna\u00eblle","family":"Marin","sequence":"additional","affiliation":[{"name":"Medical Physics Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basile","family":"Stamatopoulos","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Cell Therapy, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"de Wind","sequence":"additional","affiliation":[{"name":"Pathology Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Sirtaine","sequence":"additional","affiliation":[{"name":"Pathology Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Demetter","sequence":"additional","affiliation":[{"name":"Pathology Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Vercruyssen","sequence":"additional","affiliation":[{"name":"Haematology Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Woff","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Karfis","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghanem E.","family":"Ghanem","sequence":"additional","affiliation":[{"name":"Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Flamen","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z\u00e9na","family":"Wimana","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"},{"name":"Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles (H.U.B), Universit\u00e9 Libre de Bruxelles (ULB), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1056\/NEJMoa1607427","article-title":"Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors","volume":"376","author":"Strosberg","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1200\/JCO.2018.78.5865","article-title":"Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With 177Lu-Dotatate in the Phase III NETTER-1 Trial","volume":"36","author":"Strosberg","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.1158\/1078-0432.CCR-16-2743","article-title":"Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors","volume":"23","author":"Brabander","year":"2017","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3390\/curroncol28010015","article-title":"Efficacy of 177Lu-Dotatate Induction and Maintenance Therapy of Various Types of Neuroendocrine Tumors: A Phase II Registry Study","volume":"28","author":"Sistani","year":"2020","journal-title":"Curr. Oncol."},{"key":"ref_5","first-page":"242","article-title":"An EANM position paper on advancing radiobiology for shaping the future of nuclear medicine","volume":"50","author":"Pouget","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.2967\/jnumed.120.248062","article-title":"Combination Strategies to Improve Targeted Radionuclide Therapy","volume":"61","author":"Chan","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s00259-019-04499-x","article-title":"Combination treatments to enhance peptide receptor radionuclide therapy of neuroendocrine tumours","volume":"47","author":"Adant","year":"2020","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"C7","DOI":"10.1530\/ERC-19-0186","article-title":"The next generation of peptide receptor radionuclide therapy","volume":"26","author":"Brabander","year":"2019","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bidakhvidi, N.A., Goffin, K., Dekervel, J., Baete, K., Nackaerts, K., Clement, P., Van Cutsem, E., Verslype, C., and Deroose, C.M. (2021). Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies. Cancers, 14.","DOI":"10.3390\/cancers14010129"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.7150\/thno.15311","article-title":"Potentiation of Peptide Receptor Radionuclide Therapy by the PARP Inhibitor Olaparib","volume":"6","author":"Nonnekens","year":"2016","journal-title":"Theranostics"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Feijtel, D., Reuvers, T.G.A., Serooskerken, C.v.T.-V., de Ridder, C.M.A., Stuurman, D.C., de Blois, E., Verkaik, N.S., de Bruijn, P., Koolen, S.L.W., and de Jong, M. (2023). In Vivo Efficacy Testing of Peptide Receptor Radionuclide Therapy Radiosensitization Using Olaparib. Cancers, 15.","DOI":"10.3390\/cancers15030915"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10196","DOI":"10.1038\/s41598-020-67199-9","article-title":"Enhancing the anti-tumour activity of 177 Lu-DOTA-octreotate radionuclide therapy in somatostatin receptor-2 expressing tumour models by targeting PARP","volume":"10","author":"Cullinane","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/WOX.0b013e3182439613","article-title":"Oxidative Stress and Antioxidant Defense","volume":"5","author":"Birben","year":"2012","journal-title":"World Allergy Organ. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.nucmedbio.2021.03.006","article-title":"Investigating intrinsic radiosensitivity biomarkers to peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE in a panel of cancer cell lines","volume":"96\u201397","author":"Delbart","year":"2021","journal-title":"Nucl. Med. Biol."},{"key":"ref_15","first-page":"287","article-title":"First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid","volume":"54","author":"Ighodaro","year":"2018","journal-title":"Alex. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0065-2571(93)90006-Y","article-title":"Role of glutathione in cellular resistance to alkylating agents","volume":"33","author":"Colvin","year":"1993","journal-title":"Adv. Enzyme Regul."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/jnc.14250","article-title":"Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis","volume":"144","author":"Zhu","year":"2018","journal-title":"J. Neurochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0009-2797(88)90030-0","article-title":"Enhanced potentiation of cisplatin cytotoxicity in human ovarian carcinoma cells by prolonged glutathione depletion","volume":"65","author":"Andrews","year":"1988","journal-title":"Chem. Biol. Interact."},{"key":"ref_19","first-page":"5383","article-title":"Effect of glutathione-modulating compounds on platinum compounds-induced cytotoxicity in human glioma cell lines","volume":"19","author":"Iida","year":"1999","journal-title":"Anticancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e65150","DOI":"10.7554\/eLife.65150","article-title":"Resistance to different anthracycline chemotherapeutics elicits distinct and actionable primary metabolic dependencies in breast cancer","volume":"10","author":"McGuirk","year":"2021","journal-title":"eLife"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7512","DOI":"10.1038\/sj.onc.1206951","article-title":"Strategies for reversing drug resistance","volume":"22","author":"Fojo","year":"2003","journal-title":"Oncogene"},{"key":"ref_22","first-page":"1961","article-title":"d,l-buthionine-(S,R)-sulfoximine potentiates in vivo the therapeutic efficacy of doxorubicin against multidrug resistance protein-expressing tumors","volume":"2","author":"Vanhoefer","year":"1996","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7558","DOI":"10.1016\/S0021-9258(18)35980-5","article-title":"Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine)","volume":"254","author":"Griffith","year":"1979","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13704","DOI":"10.1016\/S0021-9258(18)33504-X","article-title":"Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione synthesis","volume":"257","author":"Griffith","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0009-2797(97)00164-6","article-title":"l-S,R-buthionine sulfoximine: Historical development and clinical issues","volume":"111\u2013112","author":"Bailey","year":"1998","journal-title":"Chem. Biol. Interact."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/BF00173503","article-title":"Cytotoxic effects of glutathione synthesis inhibition by L-buthionine-(SR)-sulfoximine on human and murine tumor cells","volume":"4","author":"Dorr","year":"1986","journal-title":"Investig. New Drugs"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e229","DOI":"10.1038\/bcj.2014.45","article-title":"The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma","volume":"4","author":"Tagde","year":"2014","journal-title":"Blood Cancer J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1182\/blood.V93.5.1724","article-title":"The somatostatin analog octreotide inhibits growth of interleukin-6 (IL-6)-dependent and IL-6-independent human multiple myeloma cell lines","volume":"93","author":"Janson","year":"1999","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1756-9966-28-77","article-title":"Somatostatin and opioid receptors do not regulate proliferation or apoptosis of the human multiple myeloma U266 cells","volume":"28","author":"Kerros","year":"2009","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/RLU.0b013e31828e9722","article-title":"68Ga-DOTANOC somatostatin receptor PET-CT imaging in multiple myeloma","volume":"39","author":"Sharma","year":"2014","journal-title":"Clin. Nucl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s00259-009-1199-5","article-title":"Somatostatin receptor scintigraphy might be useful for detecting skeleton abnormalities in patients with multiple myeloma and plasmacytoma","volume":"37","author":"Agool","year":"2010","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/MNM.0000000000000610","article-title":"The role of 68Ga-DOTA-TATE PET\/CT scanning in the evaluation of patients with multiple myeloma: Preliminary results","volume":"38","author":"Sonmezoglu","year":"2017","journal-title":"Nucl. Med. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Helgebostad, R., Revheim, M.-E., Johnsrud, K., Amlie, K., Alavi, A., and Connelly, J.P. (2022). Clinical Applications of Somatostatin Receptor (Agonist) PET Tracers beyond Neuroendocrine Tumors. Diagnostics, 12.","DOI":"10.3390\/diagnostics12020528"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/1475-2867-13-78","article-title":"Functional features of cancer stem cells in melanoma cell lines","volume":"13","author":"Zimmerer","year":"2013","journal-title":"Cancer Cell Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.ejca.2014.01.021","article-title":"Prominent role of cyclic adenosine monophosphate signalling pathway in the sensitivity of WTBRAF\/WTNRAS melanoma cells to vemurafenib","volume":"50","author":"Krayem","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.cell.2018.06.025","article-title":"Toward Minimal Residual Disease-Directed Therapy in Melanoma","volume":"174","author":"Rambow","year":"2018","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"20160474","DOI":"10.1259\/bjr.20160474","article-title":"The changing paradigm of tumour response to irradiation","volume":"90","author":"Hill","year":"2017","journal-title":"Br. J. Radiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejmp.2018.11.001","article-title":"A dosimetry procedure for organs-at-risk in 177Lu peptide receptor radionuclide therapy of patients with neuroendocrine tumours","volume":"56","author":"Marin","year":"2018","journal-title":"Phys. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2131\/jts.28.455","article-title":"A novel model of continuous depletion of glutathione in mice treated with L-buthionine (S,R)-sulfoximine","volume":"28","author":"Watanabe","year":"2003","journal-title":"J. Toxicol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/BF00300234","article-title":"Determination of subcutaneous tumor size in athymic (nude) mice","volume":"24","author":"Tomayko","year":"1989","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1080\/01478885.2015.1117190","article-title":"Optimized method for murine bone marrow collection, fixation and staining for microscopic evaluation","volume":"39","author":"Larson","year":"2016","journal-title":"J. Histotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1177\/0192623310396907","article-title":"Best practices for evaluation of bone marrow in nonclinical toxicity studies","volume":"39","author":"Reagan","year":"2011","journal-title":"Toxicol. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/0360-3016(89)90308-8","article-title":"The effect of glutathione (GSH) depletion in vivo by buthionine sulfoximine (BSO) on the radiosensitization of SR 2508","volume":"16","author":"Kramer","year":"1989","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/0272-0590(85)90173-3","article-title":"Effects of the long-term depletion of reduced glutathione in mice administered l-buthionine-S,R-sulfoximine","volume":"5","author":"Sun","year":"1985","journal-title":"Fundam. Appl. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1002\/pbc.25994","article-title":"A Phase I New Approaches to Neuroblastoma Therapy Study of Buthionine Sulfoximine and Melphalan With Autologous Stem Cells for Recurrent\/Refractory High-Risk Neuroblastoma","volume":"63","author":"Villablanca","year":"2016","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1200\/JCO.1994.12.1.194","article-title":"Phase I clinical trial of intravenous L-buthionine sulfoximine and melphalan: An attempt at modulation of glutathione","volume":"12","author":"Bailey","year":"1994","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1200\/JCO.1996.14.1.249","article-title":"Phase I trial of buthionine sulfoximine in combination with melphalan in patients with cancer","volume":"14","author":"Hamilton","year":"1996","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1093\/jnci\/89.23.1789","article-title":"Phase I Study of Continuous-Infusion l\u2014S,R-Buthionine Sulfoximine With Intravenous Melphalan","volume":"89","author":"Bailey","year":"1997","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_49","first-page":"593","article-title":"Biodistribution and Dosimetry of 177Lu-Labeled [DOTA0,Tyr3]Octreotate in Male Nude Mice with Human Small Cell Lung Cancer","volume":"18","author":"Schmitt","year":"2003","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_50","first-page":"174","article-title":"Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2","volume":"27","author":"Dalmo","year":"2012","journal-title":"Oncol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00259-014-2893-5","article-title":"Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: The value and limitations of clinical factors","volume":"42","author":"Bodei","year":"2015","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00259-015-3193-4","article-title":"Subacute haematotoxicity after PRRT with 177Lu-DOTA-octreotate: Prognostic factors, incidence and course","volume":"43","author":"Bergsma","year":"2016","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5606","DOI":"10.1073\/pnas.76.11.5606","article-title":"Glutathione: Interorgan translocation, turnover, and metabolism","volume":"76","author":"Griffith","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0305-0491(96)83706-0","article-title":"Diurnal variability of cysteine and glutathione content in the pancreas and liver of the mouse","volume":"114","author":"Rozin","year":"1996","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF00684950","article-title":"Melphalan-induced toxicity in nude mice following pretreatment with buthionine sulfoximine","volume":"28","author":"Skapek","year":"1991","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s00277-012-1653-5","article-title":"Morphology and quantitative composition of hematopoietic cells in murine bone marrow and spleen of healthy subjects","volume":"92","author":"Yang","year":"2013","journal-title":"Ann. Hematol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.nucmedbio.2012.02.003","article-title":"Nephrotoxicity profiles and threshold dose values for [177Lu]-DOTATATE in nude mice","volume":"39","author":"Svensson","year":"2012","journal-title":"Nucl. Med. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1007\/s00259-005-1877-x","article-title":"111In-labelled somatostatin analogues in a rat tumour model: Somatostatin receptor status and effects of peptide receptor radionuclide therapy","volume":"32","author":"Capello","year":"2005","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/1097-0215(20010601)92:5<628::AID-IJC1244>3.0.CO;2-L","article-title":"[177Lu-DOTA0,Tyr3]octreotate for somatostatin receptor-targeted radionuclide therapy","volume":"92","author":"Breeman","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_60","first-page":"5385","article-title":"Pharmacokinetics of buthionine sulfoximine (NSC 326231) and its effect on melphalan-induced toxicity in mice","volume":"49","author":"Smith","year":"1989","journal-title":"Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/8\/2332\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:17:13Z","timestamp":1760123833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/8\/2332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,17]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["cancers15082332"],"URL":"https:\/\/doi.org\/10.3390\/cancers15082332","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,17]]}}}