{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T11:55:04Z","timestamp":1791719704569,"version":"4.3.4"},"reference-count":179,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Cyprus"},{"name":"Postgraduate Research Institute of Science, Technology, Environment and Medicine"},{"name":"a non-profit, charitable organization"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Scandium (Sc) isotopes have recently attracted significant attention in the search for new radionuclides with potential uses in personalized medicine, especially in the treatment of specific cancer patient categories. In particular, Sc-43 and Sc-44, as positron emitters with a satisfactory half-life (3.9 and 4.0 h, respectively), are ideal for cancer diagnosis via Positron Emission Tomography (PET). On the other hand, Sc-47, as an emitter of beta particles and low gamma radiation, may be used as a therapeutic radionuclide, which also allows Single-Photon Emission Computed Tomography (SPECT) imaging. As these scandium isotopes follow the same biological pathway and chemical reactivity, they appear to fit perfectly into the \u201ctheranostic pair\u201d concept. A step-by-step description, initiating from the moment of scandium isotope production and leading up to their preclinical and clinical trial applications, is presented. Recent developments related to the nuclear reactions selected and employed to produce the radionuclides Sc-43, Sc-44, and Sc-47, the chemical processing of these isotopes and the main target recovery methods are also included. Furthermore, the radiolabeling of the leading chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and its structural analogues with scandium is also discussed and the advantages and disadvantages of scandium complexation are evaluated. Finally, a review of the preclinical studies and clinical trials involving scandium, as well as future challenges for its clinical uses and applications, are presented.<\/jats:p>","DOI":"10.3390\/ijms25115954","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T10:42:34Z","timestamp":1717065754000},"page":"5954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Towards Clinical Development of Scandium Radioisotope Complexes for Use in Nuclear Medicine: Encouraging Prospects with the Chelator 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTA) and Its Analogues"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6896-2877","authenticated-orcid":false,"given":"Ioannis","family":"Ioannidis","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Cyprus, 2109 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Lefkaritis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cyprus, 2109 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6106-9904","authenticated-orcid":false,"given":"Savvas N.","family":"Georgiades","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cyprus, 2109 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-6395","authenticated-orcid":false,"given":"Ioannis","family":"Pashalidis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cyprus, 2109 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3364-7340","authenticated-orcid":false,"given":"George J.","family":"Kontoghiorghes","sequence":"additional","affiliation":[{"name":"Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3021 Limassol, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.2174\/18744729MTEwiMjka0","article-title":"IAEA activities on 67Cu, 186Re, 47Sc theranostic radionuclides and radiopharmaceuticals","volume":"14","author":"Jalilian","year":"2021","journal-title":"Curr. Radiopharm."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Srivastava, S.C., and Mausner, L.F. (2013). Therapeutic radionuclides: Production, physical characteristics, and applications. Therapeutic Nuclear Medicine, Springer.","DOI":"10.1007\/174_2012_782"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1007\/s00259-019-04624-w","article-title":"Paediatric Nuclear Medicine Practice: An International Survey by the IAEA","volume":"47","author":"Poli","year":"2020","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_4","first-page":"11","article-title":"Radiopharmaceuticals for diagnosis in nuclear medicine: A short review","volume":"44","author":"Payolla","year":"2019","journal-title":"Ecl\u00e9tica Qu\u00edmica"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ilem-Ozdemir, D., Gundogdu, E.A., Ekinci, M., Ozgenc, E., and Asikoglu, M. (2019). Nuclear medicine and radiopharmaceuticals for molecular diagnosis. Biomedical Applications of Nanoparticles, William Andrew Publishing.","DOI":"10.1016\/B978-0-12-816506-5.00017-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.7150\/ijms.3635","article-title":"Cancer and Radiation Therapy: Current Advances and Future Directions","volume":"9","author":"Baskar","year":"2012","journal-title":"Int. J. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/nrd4003","article-title":"Strategies for optimizing the response of cancer and normal tissues to radiation","volume":"12","author":"Moding","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104988","DOI":"10.1016\/j.pnucene.2023.104988","article-title":"Radiological characterization plan for decommissioning IFIN-HH\u2019s Cyclotron","volume":"168","author":"Ionescu","year":"2024","journal-title":"Prog. Nucl. Energy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nrc3007","article-title":"Strategies to improve radiotherapy with targeted drugs","volume":"11","author":"Begg","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1007\/s00259-012-2330-6","article-title":"The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours","volume":"40","author":"Zaknun","year":"2013","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40001-023-01627-0","article-title":"Radiopharmaceuticals: Navigating the frontier of precision medicine and therapeutic innovation","volume":"29","author":"Dhoundiyal","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Talip, Z., Favaretto, C., Geistlich, S., and van der Meulen, N.P. (2020). A Step-by-Step Guide for the Novel Radiometal Production for Medical Applications: Case Studies with 68Ga, 44Sc, 177Lu and 161Tb. Molecules, 25.","DOI":"10.3390\/molecules25040966"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J. (2020). Advances on Chelation and Chelator Metal Complexes in Medicine. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072499"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3109\/03630269.2011.578950","article-title":"Interactions of hydroxycarbamide (hydroxyurea) with iron and copper: Implications on toxicity and therapeutic strategies","volume":"35","author":"Konstantinou","year":"2011","journal-title":"Hemoglobin"},{"key":"ref_15","first-page":"998","article-title":"Molecular factors affecting the complex formation between deferiprone (L1) and Cu(II). Possible implications on efficacy and toxicity","volume":"51","author":"Pashalidis","year":"2001","journal-title":"Arzneimittelforschung"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1432-1033.1971.tb01439.x","article-title":"The binding of scandium ions to transferrin in vivo and in vitro","volume":"21","author":"Perkins","year":"1971","journal-title":"Eur. J. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1517\/13543784.2013.787408","article-title":"Potential clinical applications of chelating drugs in diseases targeting transferrin-bound iron and other metals","volume":"22","author":"Kontoghiorghe","year":"2013","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/03630260600642450","article-title":"Iron mobilization from transferrin and non-transferrin-bound-iron by deferiprone. Implications in the treatment of thalassemia, anemia of chronic disease, cancer and other conditions","volume":"30","author":"Kontoghiorghes","year":"2006","journal-title":"Hemoglobin"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12223","DOI":"10.1021\/acs.inorgchem.3c00314","article-title":"Insights into Actinium Complexes with Tetraacetates\u2500AcBATA versus AcDOTA: Thermodynamic, Structural, and Labeling Properties","volume":"62","author":"Matazova","year":"2023","journal-title":"Inorg. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.cbpa.2021.03.001","article-title":"Emerging chelators for nuclear imaging","volume":"63","author":"Sneddon","year":"2021","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"957172","DOI":"10.3389\/fendo.2022.957172","article-title":"Response to targeted radionuclide therapy with [131I]MIBG AND [177Lu]Lu-DOTA-TATE according to adrenal vs. extra-adrenal primary location in metastatic paragangliomas and pheochromocytomas: A systematic review","volume":"13","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s40336-019-00326-3","article-title":"Recent developments of prostate-specific membrane antigen (PSMA)-specific radiopharmaceuticals for precise imaging and therapy of prostate cancer: An overview","volume":"7","author":"Okarvi","year":"2019","journal-title":"Clin. Transl. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jensen, S.B. (2024). Radioactive Molecules 2021\u20132022. Molecules, 29.","DOI":"10.3390\/molecules29010265"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mohapatra, S.K., and Dash, A.K. (2024). Special Dosage Forms and Drug Delivery Systems. Pharmaceutics, Academic Press. [2nd ed.].","DOI":"10.1016\/B978-0-323-99796-6.00018-7"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R99","DOI":"10.1088\/0031-9155\/51\/13\/R07","article-title":"The early years of single photon emission computed tomography (SPECT): An anthology of selected reminiscences","volume":"51","author":"Jaszczak","year":"2006","journal-title":"Phys. Med. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Raju, G., Nayak, S., Acharya, N., Sunder, M., Kistenev, Y., and Mazumder, N. (2024). Exploring the future of regenerative medicine: Unveiling the potential of optical microscopy for structural and functional imaging of stem cells. J. Biophotonics, 17.","DOI":"10.1002\/jbio.202300360"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1002\/adhm.201500126","article-title":"Recent Advances in Targeted, Self-Assembling Nanoparticles to Address Vascular Damage Due to Atherosclerosis","volume":"4","author":"Chung","year":"2015","journal-title":"Adv. Healthc. Mater."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lamba, M., Singh, P.R., Bandyopadhyay, A., and Goswami, A. (RSC Med. Chem., 2024). Synthetic 18F labeled biomolecules that are selective and promising for PET imaging: Major advances and applications, RSC Med. Chem., advance article.","DOI":"10.1039\/D4MD00033A"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"van der Meulen, N.P., Strobel, K., and Lima, T.V.M. (2021). New Radionuclides and Technological Advances in SPECT and PET Scanners. Cancers, 13.","DOI":"10.3390\/cancers13246183"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41366-023-01394-2","article-title":"Metabolic interactions between organs in overweight and obesity using total-body positron emission tomography","volume":"48","author":"Lu","year":"2024","journal-title":"Int. J. Obes."},{"key":"ref_31","first-page":"661","article-title":"PET: The Merging of Biology and Imaging into Molecular Imaging","volume":"41","author":"Phelps","year":"2000","journal-title":"J. Nucl. Med."},{"key":"ref_32","unstructured":"von Schulthess, G.K. (2007). Molecular Anatomic Imaging: PET-CT and SPECT-CT Integrated Modality Imaging, Lippincott Williams & Wilkins."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1148\/radiol.2241011254","article-title":"Recurrent laryngeal nerve palsy in patients with lung cancer: Detection with PET-CT image fusion\u2014Report of six cases","volume":"224","author":"Kamel","year":"2002","journal-title":"Radiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1148\/radiographics.19.1.g99ja0761","article-title":"Pitfalls in oncologic diagnosis with FDG PET imaging: Physiologic and benign variants","volume":"19","author":"Shreve","year":"1999","journal-title":"Radiographics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.2967\/jnumed.115.156711","article-title":"Beyond 18F-FDG: Characterization of PET\/CT and PET\/MR scanners for a comprehensive set of positron emitters of growing application\u201418F, 11C, 89Zr, 124I, 68Ga, and 90Y","volume":"56","author":"Soderlund","year":"2015","journal-title":"J. Nucl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.cpet.2020.06.009","article-title":"Prospects and clinical perspectives of total-body PET imaging using plastic scintillators","volume":"15","author":"Moskal","year":"2020","journal-title":"PET Clin."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Raeymaeckers, S., De Brucker, Y., Vanderhasselt, T., Buls, N., and De Mey, J. (2021). Detection of parathyroid adenomas with multiphase 4DCT: Towards a true four-dimensional technique. BMC Med. Imaging, 21.","DOI":"10.1186\/s12880-021-00597-1"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Naqvi, S., and Imran, M.B. (2021). Single-Photon Emission Computed Tomography (SPECT) Radiopharmaceuticals. Medical Isotopes, IntechOpen.","DOI":"10.5772\/intechopen.93449"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"R145","DOI":"10.1088\/0031-9155\/56\/17\/R01","article-title":"SPECT detectors: The Anger Camera and beyond","volume":"56","author":"Peterson","year":"2011","journal-title":"Phys. Med. Biol."},{"key":"ref_40","unstructured":"Lodge, M.A., and Frey, E.C. (2014). Nuclear Medicine Imaging Devices, Chapter 11, IAEA."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108879","DOI":"10.1016\/j.nucmedbio.2024.108879","article-title":"Advancements in the development of radiopharmaceuticals for nuclear medicine applications in the treatment of bone metastases","volume":"130\u2013131","author":"Dyer","year":"2024","journal-title":"Nucl. Med. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bisogni, M.G. (2024). Quality assurance in particle therapy with PET. Monte Carlo in Heavy Charged Particle Therapy, CRC Press.","DOI":"10.1201\/9781003023920-7"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.nucmedbio.2015.05.005","article-title":"Cyclotron production of (44)Sc: From bench to bedside","volume":"42","author":"Bunka","year":"2015","journal-title":"Nucl. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/jlcr.3622","article-title":"Aligning physics and physiology: Engineering antibodies for radionuclide delivery","volume":"61","author":"Tsai","year":"2018","journal-title":"J. Labelled Comp. Radiopharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.addr.2008.04.006","article-title":"Bifunctional Coupling Agents for Radiolabeling of Biomolecules and Target-Specific Delivery of Metallic Radionuclides","volume":"60","author":"Liu","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gudkov, S.V., Shilyagina, N.Y., Vodeneev, V.A., and Zvyagin, A.V. (2016). Targeted Radionuclide Therapy of Human Tumors. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010033"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1631\/jzus.B1400131","article-title":"Therapeutic radionuclides in nuclear medicine: Current and future prospects","volume":"15","author":"Yeong","year":"2014","journal-title":"J. Zhejiang Univ. Sci. B (Biomed. Biotechnol.)"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"430276","DOI":"10.1155\/2013\/430276","article-title":"Investigation of attenuation correction for small-animal single photon emission computed tomography","volume":"2013","author":"Lee","year":"2013","journal-title":"Comput. Math. Methods Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lange, R., Schreuder, N., and Hendrikse, H. (2023). Radiopharmaceuticals. Practical Pharmaceutics: An International Guideline for the Preparation, Care and Use of Medicinal Products, Springer International Publishing.","DOI":"10.1007\/978-3-031-20298-8_23"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41573-020-0073-9","article-title":"Radiopharmaceutical therapy in cancer: Clinical advances and challenges","volume":"19","author":"Sgouros","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/jlcr.3582","article-title":"Re-thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals","volume":"61","author":"Notni","year":"2018","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4821","DOI":"10.2147\/OTT.S140671","article-title":"Theranostics in nuclear medicine practice","volume":"10","author":"Yordanova","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Velikyan, I. (2014). Radionuclides for imaging and therapy in oncology. Cancer Theranostics, Academic Press.","DOI":"10.1016\/B978-0-12-407722-5.00017-7"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1021\/ar2001777","article-title":"Responsive theranostic systems: Integration of diagnostic imaging agents and responsive controlled release drug delivery carriers","volume":"44","author":"Liechty","year":"2011","journal-title":"Acc. Chem. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s10967-018-6238-x","article-title":"New developments in the production of theranostic pairs of radionuclides","volume":"318","author":"Qaim","year":"2018","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/09506608.2015.1137692","article-title":"The scandium effect in multicomponent alloys","volume":"61","author":"Riva","year":"2016","journal-title":"Int. Mater. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e202114203","DOI":"10.1002\/ange.202114203","article-title":"An Unusual Pair: Facile Formation and In Vivo Validation of Robust Sc\u201318F Ternary Complexes for Molecular Imaging","volume":"134","author":"Whetter","year":"2022","journal-title":"Angew. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"20180074","DOI":"10.1259\/bjr.20180074","article-title":"Scandium and terbium radionuclides for radiotheranostics: Current state of development towards clinical application","volume":"91","author":"Domnanich","year":"2018","journal-title":"Brit. J. Radiol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Trencs\u00e9nyi, G., and K\u00e9pes, Z. (2023). Scandium-44: Diagnostic Feasibility in Tumor-Related Angiogenesis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087400"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s41181-021-00131-2","article-title":"Production of scandium radionuclides for theranostic applications: Towards standardization of quality requirements","volume":"6","author":"Mikolajczak","year":"2021","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.apradiso.2013.01.039","article-title":"Clinical Applications of Gallium-68","volume":"76","author":"Banerjee","year":"2013","journal-title":"Appl. Radiat. Isot."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s41181-017-0033-9","article-title":"Production and separation of 43Sc for radiopharmaceutical purposes","volume":"2","author":"Domnanich","year":"2017","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Mas\u0142owska, K., Redkiewicz, P., Halik, P.K., Witkowska, E., Tymecka, D., Walczak, R., Choi\u0144ski, J., Misicka, A., and Gniazdowska, E. (2023). Scandium-44 Radiolabeled Peptide and Peptidomimetic Conjugates Targeting Neuropilin-1 Co-Receptor as Potential Tools for Cancer Diagnosis and Anti-Angiogenic Therapy. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020564"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1053\/j.semnuclmed.2019.06.002","article-title":"From bench to bedside\u2014The bad Berka experience with first-in-human studies","volume":"49","author":"Zhang","year":"2019","journal-title":"Semin. Nucl. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s41181-024-00239-1","article-title":"Implementing Ac-225 labelled radiopharmaceuticals: Practical considerations and (pre-) clinical perspectives","volume":"9","author":"Hooijman","year":"2024","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.2967\/jnumed.114.141614","article-title":"Promising Prospects for 44Sc-\/47Sc-Based Theragnostics: Application of 47Sc for Radionuclide Tumor Therapy in Mice","volume":"55","author":"Bunka","year":"2014","journal-title":"J. Nucl. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"110943","DOI":"10.1016\/j.apradiso.2023.110943","article-title":"Photonuclear production of 47Ca for 47Ca\/47Sc generator from natural CaCO3 targets","volume":"200","author":"Kankanamalage","year":"2023","journal-title":"Appl. Radiat. Isot."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/jlcr.3770","article-title":"Radiometals for imaging and theranostics, current production, and future perspectives","volume":"62","author":"Mikolajczak","year":"2019","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1524\/ract.2010.1701","article-title":"A 44Ti\/44Sc radionuclide generator for potential application of 44Sc-based PET-radiopharmaceuticals","volume":"98","author":"Filosofov","year":"2010","journal-title":"Radiochim. Acta"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2174\/1874471011205030187","article-title":"Scandium-44: Benefits of a Long-Lived PET Radionuclide Available from the 44Ti\/44Sc Generator System","volume":"5","author":"Roesch","year":"2012","journal-title":"Curr. Radiopharm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1016\/j.apradiso.2010.04.003","article-title":"Post-elution processing of 44Ti\/44Sc generator-derived 44Sc for clinical application","volume":"68","author":"Pruszynki","year":"2010","journal-title":"Appl. Radiat. Isot."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"110588","DOI":"10.1016\/j.apradiso.2022.110588","article-title":"Evaluation of hydroxamate-based resins towards a more clinically viable 44Ti\/44Sc radionuclide generator","volume":"192","author":"Gajecki","year":"2023","journal-title":"Appl. Radiat. Isot."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.apradiso.2014.09.020","article-title":"Separation of cyclotron-produced (44)Sc from a natural calcium target using a dipentyl pentylphosphonate functionalized extraction resin","volume":"95","author":"Valdovinos","year":"2015","journal-title":"Appl. Radiat. Isot."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kilian, K., and Pyrzy\u0144ska, K. (2023). Scandium Radioisotopes\u2014Toward New Targets and Imaging Modalities. Molecules, 28.","DOI":"10.3390\/molecules28227668"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1524\/ract.2013.2032","article-title":"Cyclotron production of 44Sc for clinical application","volume":"101","author":"Krajewski","year":"2013","journal-title":"Radiochim. Acta"},{"key":"ref_76","unstructured":"Koning, A.J., Rochman, D., Kopecky, J., Sublet, J.C., Bauge, E., Hilaire, S., Romain, P., Morillon, B., Duarte, H., and van der Marck, S. (2015). TALYS-Based Evaluated Nuclear Data Library, American Nuclear Society. TENDL."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s41181-018-0038-z","article-title":"Production of novel diagnostic radionuclides in small medical cyclotrons","volume":"3","author":"Synowiecki","year":"2018","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"van der Meulen, N.P., Hasler, R., Talip, Z., Grundler, P.V., Favaretto, C., Umbricht, C.A., M\u00fcller, C., Dellepiane, G., Carzaniga, T.S., and Braccini, S. (2020). Developments toward the implementation of (44)Sc production at a medical cyclotron. Molecules, 25.","DOI":"10.3390\/molecules25204706"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.apradiso.2018.09.025","article-title":"Production of Sc medical radioisotopes with proton and deuteron beams","volume":"142","author":"Sitarz","year":"2018","journal-title":"Appl. Radiat. Isot."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.apradiso.2016.07.001","article-title":"Production of medical Sc radioisotopes with an alpha particle beam","volume":"118","author":"Szkliniarz","year":"2016","journal-title":"Appl. Radiat. Isot."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.apradiso.2016.07.017","article-title":"Production of scandium-43 and -47 from a powdery calcium oxide target via the (nat\/44)Ca(alpha,x)-channel","volume":"116","author":"Minegishi","year":"2016","journal-title":"Appl. Radiat. Isot."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.apradiso.2018.12.031","article-title":"Measurement of the (43)Sc production cross-section with a deuteron beam","volume":"145","author":"Carzaniga","year":"2019","journal-title":"Appl. Radiat. Isot."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Juget, F., Dur\u00e1n, T., Nedjadi, Y., Talip, Z., Grundler, P.V., Favaretto, C., Casolaro, P., Dellepiane, G., Braccini, S., and Bailat, C. (2023). Activity Measurement of 44Sc and Calibration of Activity Measurement Instruments on Production Sites and Clinics. Molecules, 28.","DOI":"10.3390\/molecules28031345"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.apradiso.2012.04.030","article-title":"Cyclotron produced 44gSc from natural calcium","volume":"70","author":"Severin","year":"2012","journal-title":"Appl. Radiat. Isot."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.chroma.2016.11.047","article-title":"Separation of 44Ti from proton irradiated scandium by using solid-phase extraction chromatography and design of 44Ti\/44Sc generator system","volume":"1477","author":"Radchenko","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.nucmedbio.2015.03.002","article-title":"Cyclotron production of high purity (44m,44)Sc with deuterons from (44)CaCO3 targets","volume":"42","author":"Alliot","year":"2015","journal-title":"Nucl. Med. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1167783","DOI":"10.3389\/fchem.2023.1167783","article-title":"Cyclotron production of 43Sc and 44gSc from enriched 42CaO, 43CaO, and 44CaO targets","volume":"11","author":"Becker","year":"2023","journal-title":"Front. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"110921","DOI":"10.1016\/j.apradiso.2023.110921","article-title":"Alpha-induced production and robust radiochemical separation of 43Sc as an emerging radiometal for formulation of PET radiopharmaceuticals","volume":"199","author":"Chakravarty","year":"2023","journal-title":"Appl. Radiat. Isot."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"156","DOI":"10.4103\/0971-6203.165078","article-title":"Production, biodistribution, and dosimetry of 47Sc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid as a bone-seeking radiopharmaceutical","volume":"40","author":"Fathi","year":"2015","journal-title":"J. Med. Phys."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"El-Din, A.M.S., Rizk, H.E., and Attallah, M.F. (2023). Purification of Carrier-Free 47Sc of Biomedical Interest: Selective Separation Study from natCa(n,\u03b3). Separations, 10.","DOI":"10.3390\/separations10010008"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10967-021-07620-3","article-title":"Theoretical and experimental investigations of Sc-47 production at Egyptian Second Research Reactor (ETRR-2)","volume":"328","author":"Gizawy","year":"2021","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1515\/ract-2018-3070","article-title":"Feasibility study on production of Sc-47 from neutron irradiated Ca target for cancer theranostics applications","volume":"108","author":"Gizawy","year":"2020","journal-title":"Radiochim. Acta"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s10967-009-0370-6","article-title":"Separation of no-carrier-added radioactive scandium from neutron irradiated titanium","volume":"283","author":"Bokhari","year":"2009","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1524\/ract.2012.1938","article-title":"New separation method of no-carrier-added 47Sc from titanium targets","volume":"100","author":"Majkowska","year":"2012","journal-title":"Radiochim. Acta"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.apradiso.2016.09.004","article-title":"Production and purification of Scandium-47: A potential radioisotope for cancer theranostics","volume":"118","author":"Sadeghi","year":"2016","journal-title":"Appl. Radiat. Isot."},{"key":"ref_96","first-page":"388","article-title":"Production and evaluation of Sc-47 for radioimmunotherapy","volume":"32","author":"Mausner","year":"1993","journal-title":"J. Labelled Comp. Radiopharm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.apradiso.2019.05.020","article-title":"Comparison of separation methods for 47Ca\/47Sc radionuclide generator","volume":"151","author":"Pawlak","year":"2019","journal-title":"Appl. Radiat. Isot."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.apradiso.2015.04.012","article-title":"Sc-47 production from titanium targets using electron linacs","volume":"102","author":"Mamtimin","year":"2015","journal-title":"Appl. Radiat. Isot."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.apradiso.2017.11.007","article-title":"Electron linear accelerator production and purification of scandium-47 from titanium dioxide targets","volume":"131","author":"Rotsch","year":"2018","journal-title":"Appl. Radiat. Isot."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.apradiso.2019.07.007","article-title":"Investigations of proton and deuteron induced nuclear reactions on natural and enriched titanium, calcium and vanadium targets, with special reference to the production of (47)Sc","volume":"152","author":"Jafari","year":"2019","journal-title":"Appl. Radiat. Isot."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10967-015-4039-z","article-title":"Accelerator-based photoproduction of promising beta-emitters 67Cu and 47Sc","volume":"305","author":"Starovoitova","year":"2015","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"109934","DOI":"10.1016\/j.apradiso.2021.109934","article-title":"High purity 47Sc production using high-energy photons and natural vanadium targets","volume":"178","author":"Snow","year":"2021","journal-title":"Appl. Radiat. Isot."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5623","DOI":"10.1007\/s10967-022-08611-8","article-title":"Exploring rapid chemical separations of Sc-47 produced from photonuclear reactions on natural vanadium targets","volume":"331","author":"Meiers","year":"2022","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"31","DOI":"10.5005\/jp-journals-10028-1054","article-title":"A Bridge not too Far: Personalized Medicine with the use of Theragnostic Radiopharmaceuticals","volume":"47","author":"Srivastava","year":"2013","journal-title":"J. Postgrad. Med. Edu Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s10967-017-5321-z","article-title":"(47)Sc production development by cyclotron irradiation of (48)Ca","volume":"313","author":"Misiak","year":"2017","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.apradiso.2018.10.015","article-title":"Cross-section measurement of 44mSc, 47Sc, 48Sc and 47Ca for an optimized 47Sc production with an 18 MeV medical PET cyclotron","volume":"143","author":"Carzaniga","year":"2019","journal-title":"Appl. Radiat. Isot."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.nimb.2016.05.015","article-title":"Activation cross-sections of proton induced reactions on vanadium in the 37-65 MeV energy range","volume":"381","author":"Ditroi","year":"2016","journal-title":"Nucl. Instrum. Meth B"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"127400","DOI":"10.1016\/j.seppur.2024.127400","article-title":"Robust electrochemical method for separation of theranostic 44Sc\/47Sc pair of radiometals","volume":"345","author":"Patra","year":"2024","journal-title":"Sep. Purif. Technol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1007\/s10967-019-06844-8","article-title":"Production of 47Sc with natural vanadium targets: Results of the PASTA project","volume":"322","author":"Pupillo","year":"2019","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Mamis, E., Duchemin, C., Berlin, V., Bernerd, C., Bovigny, M., Chevallay, E., Crepieux, B., Gadelshin, V.M., Heinke, R., and Hernandez, R.M. (2024). Target Development towards First Production of High-Molar-Activity 44gSc and 47Sc by Mass Separation at CERN-MEDICIS. Pharmaceuticals, 17.","DOI":"10.3390\/ph17030390"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1515\/ract-2022-0082","article-title":"Development of purification of no-carrier-added 47Sc of theranostic interest: Selective separation study from the natTi(n,p) process","volume":"3","author":"Rizk","year":"2023","journal-title":"Radiochim. Acta"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40658-015-0136-x","article-title":"Cyclotron production of (43)Sc for PET imaging","volume":"2","author":"Walczak","year":"2015","journal-title":"EJNMMI Phys."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0969-8043(97)00040-7","article-title":"Radionuclide development at BNL for nuclear medicine therapy","volume":"49","author":"Mausner","year":"1998","journal-title":"Appl. Radiat. Isot."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s10967-023-08783-x","article-title":"Evaluation of two extraction chromatography resins for scandium and titanium separation for medical isotope production","volume":"332","author":"McLain","year":"2023","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2967\/jnumed.120.242941","article-title":"Cyclotron Production and Separation of Scandium Radionuclides from Natural Titanium Metal and Titanium Dioxide Targets","volume":"62","author":"Loveless","year":"2021","journal-title":"J. Nucl. Med."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Lima, T.V.M., Gnesin, S., Strobel, K., P\u00e9rez, M.D.S., Roos, J.E., M\u00fcller, C., and van der Meulen, N.P. (2021). Fifty Shades of Scandium: Comparative Study of PET Capabilities Using Sc-43 and Sc-44 with Respect to Conventional Clinical Radionuclides. Diagnostics, 11.","DOI":"10.3390\/diagnostics11101826"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"127734","DOI":"10.1016\/j.seppur.2024.127734","article-title":"A perspective on molecular recognition technology for recovering critical metals from minerals and processing wastes","volume":"347","author":"Huang","year":"2024","journal-title":"Sep. Purif. Technol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.2967\/jnumed.118.213264","article-title":"Production and use of the first-row transition metal PET radionuclides (43,44)Sc, (52)Mn, and (45)Ti","volume":"59","author":"Chaple","year":"2018","journal-title":"J. Nucl. Med."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Kilian, K., Cheda, \u0141., Sitarz, M., Szkliniarz, K., Choi\u0144ski, J., and Stolarz, A. (2018). Separation of (44)Sc from natural calcium carbonate targets for synthesis of (44)Sc-DOTATATE. Molecules, 23.","DOI":"10.3390\/molecules23071787"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Saini, S., and Lapi, S.E. (2024). Titanium-45 (45Ti) Radiochemistry and Applications in Molecular Imaging. Pharmaceuticals, 17.","DOI":"10.3390\/ph17040479"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1007\/s10967-012-2188-x","article-title":"Stability of (47)Sc-complexes with acyclic polyamino-polycarboxylate ligands","volume":"295","author":"Piotrowska","year":"2013","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_122","first-page":"569","article-title":"Evaluation of cyclotron produced 43,44,47Sc from titanium (0) and titanium dioxide","volume":"1","author":"Loveless","year":"2019","journal-title":"J. Labelled Comp. Radiopharm."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/BF02047448","article-title":"Separation of carrier-free47Sc from titanium targets","volume":"157","author":"Pietrelli","year":"1992","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jinorgbio.2010.11.003","article-title":"Macrocyclic complexes of scandium radionuclides as precursors for diagnostic and therapeutic radiopharmaceuticals","volume":"105","author":"Bilewicz","year":"2011","journal-title":"J. Inorg. Biochem."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Patel, M., and Karamalidis, A. Adsorption-Based Separation and Recovery of Rare Earth Elements. Authorea Prepr., 2023.","DOI":"10.22541\/essoar.168167398.84484841\/v1"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1021\/acs.oprd.3c00070","article-title":"Practical Synthesis of Tenofovir Alafenamide Fumarate Inspired by New Retrosynthetic Disconnection Featuring a Novel Carbon\u2013Phosphorus Bond Construction Methodology","volume":"27","author":"Liu","year":"2023","journal-title":"Org. Process. Res. Dev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"105597","DOI":"10.1016\/j.hydromet.2021.105597","article-title":"High purity scandium extraction from red mud by novel simple technology","volume":"202","author":"Pasechnik","year":"2021","journal-title":"Hydrometallurgy"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s11705-017-1653-z","article-title":"Materials Sustainability for Environment: Red-Mud Treatment","volume":"11","author":"Mishra","year":"2017","journal-title":"Front. Chem. Sci. Eng."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ccr.2018.11.007","article-title":"Radiochemical processing of nuclear-reactor-produced radiolanthanides for medical applications","volume":"382","author":"Cardinaels","year":"2019","journal-title":"Coord. Chem. Rev."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.talanta.2010.01.008","article-title":"Distribution coefficients of 60 elements on TODGA resin: Application to Ca, Lu, Hf, U and Th isotope geochemistry","volume":"81","author":"Pourmand","year":"2010","journal-title":"Talanta"},{"key":"ref_131","unstructured":"Boron-Brenner, L. (2018, May 31). Development of Chemical Separation Methods Using Transition Metals for Nuclear Forensic and Medicinal Applications. Available from ProQuest Dissertations & Theses Global. (Order No. 10813737). Available online: https:\/\/www.proquest.com\/dissertations-theses\/development-chemical-separation-methods-using\/docview\/2124413447\/se-2."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1007\/s10967-016-4695-7","article-title":"A new method for separating first row transition metals and actinides from synthetic melt glass","volume":"307","author":"Roman","year":"2016","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1007\/s00259-011-2001-z","article-title":"Radiopharmaceutical development of radiolabelled peptides","volume":"39","author":"Fani","year":"2012","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1021\/cr3003104","article-title":"Radiometals for combined imaging and therapy","volume":"113","author":"Cutler","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"99606","DOI":"10.1039\/C5RA16736A","article-title":"A comparative thermodynamic study of the formation of scandium complexes with DTPA and DOTA","volume":"5","author":"Alliot","year":"2015","journal-title":"RSC Adv."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"7944","DOI":"10.1002\/chem.201402041","article-title":"Thermodynamic and Kinetic Study of Scandium(III) Complexes of DTPA and DOTA: A Step Toward Scandium Radiopharmaceuticals","volume":"20","author":"Pniok","year":"2014","journal-title":"Chem. Eur. J."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1039\/C5DT04084A","article-title":"Scandium(III) complexes of monophosphorus acid DOTA analogues: A thermodynamic and radiolabelling study with 44Sc from cyclotron and from a 44Ti\/44Sc generator","volume":"45","author":"Kerdjoudj","year":"2016","journal-title":"Dalton Trans."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Sz\u00fccs, D., Csup\u00e1sz, T., Szab\u00f3, J.P., Kis, A., Gyuricza, B., Arat\u00f3, V., Forg\u00e1cs, V., V\u00e1gner, A., Nagy, G., and Garai, I. (2022). Synthesis, Physicochemical, Labeling and In Vivo Characterization of 44Sc-Labeled DO3AM-NI as a Hypoxia-Sensitive PET Probe. Pharmaceuticals, 26.","DOI":"10.3390\/ph15060666"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.apradiso.2012.03.005","article-title":"Radiolabeling of DOTATOC with the long-lived positron emitter 44Sc","volume":"70","author":"Loktionova","year":"2012","journal-title":"Appl. Radiat. Isot."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"\u00dcnak, P., Yasak\u00e7\u0131, V., Tutun, E., Karatay, K.B., Walczak, R., Wawrowicz, K., \u017belechowska-Matysiak, K., Majkowska-Pilip, A., and Bilewicz, A. (2023). Multimodal Radiobioconjugates of Magnetic Nanoparticles Labeled with 44Sc and 47Sc for Theranostic Application. Pharmaceutics, 15.","DOI":"10.20944\/preprints202302.0418.v1"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1039\/C9SC04655K","article-title":"Chelation with a twist: A bifunctional chelator to enable room temperature radiolabeling and targeted PET imaging with scandium-44","volume":"11","author":"Vaughn","year":"2020","journal-title":"Chem. Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1002\/anie.201611207","article-title":"AAZTA: An ideal chelating agent for the development of (44) Sc PET imaging agents","volume":"56","author":"Nagy","year":"2017","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"9994","DOI":"10.1039\/D1DT03887G","article-title":"Synthesis, solid-state, solution, and theoretical characterization of an \u201cin-cage\u201d scandium-NOTA complex","volume":"51","author":"Aldrich","year":"2022","journal-title":"Dalton Trans."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Fersing, C., Masurier, N., Rubira, L., Deshayes, E., and Lisowski, V. (2022). AAZTA-derived chelators for the design of innovative radiopharmaceuticals with theranostic applications. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020234"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1021\/acs.bioconjchem.9b00225","article-title":"Functionally versatile and highly stable Chelator for (111)in and (177)Lu: Proof-of-principle prostate-specific membrane antigen targeting","volume":"30","author":"Li","year":"2019","journal-title":"Bioconjugate Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1021\/acs.inorgchem.9b03347","article-title":"[nat\/44Sc(pypa)]\u2212: Thermodynamic Stability, Radiolabeling, and Biodistribution of a Prostate-Specific-Membrane-Antigen-Targeting Conjugate","volume":"59","author":"Li","year":"2020","journal-title":"Inorg. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1016\/j.nucmedbio.2013.11.004","article-title":"Optimization of reaction conditions for the radiolabeling of DOTA and DOTA-peptide with 44m\/44Sc and experimental evidence of the feasibility of an in vivo PET generator","volume":"41","author":"Kerdjoudj","year":"2014","journal-title":"Nucl. Med. Biol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0928-0987(03)00040-X","article-title":"Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing","volume":"19","author":"Combes","year":"2003","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"854","DOI":"10.4161\/cbt.4.8.1893","article-title":"Radiolabeling and biological evaluation of DOTA-Ph-Al derivative conjugated to anti-EGFR antibody ior egf\/r3 for targeted tumor imaging and therapy","volume":"4","author":"Panwar","year":"2005","journal-title":"Cancer Biol. Ther."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1524\/ract.2011.1869","article-title":"Chemical and biological evaluation of scandium(III)-polyaminopolycarboxylate complexes as potential PET agents and radiopharmaceuticals","volume":"99","author":"Sabatie","year":"2011","journal-title":"Radiochim. Acta"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1021\/cr00039a010","article-title":"Thermodynamic and Kinetic Data for Macrocycle Interaction with Cations, Anions, and Neutral Molecules","volume":"95","author":"Izatt","year":"1995","journal-title":"Chem. Rev."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"10429","DOI":"10.1021\/jacs.1c05339","article-title":"Py-Macrodipa: A Janus Chelator Capable of Binding Medicinally Relevant Rare-Earth Radiometals of Disparate Sizes","volume":"143","author":"Hu","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"163","DOI":"10.5662\/wjm.v4.i3.163","article-title":"World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients","volume":"4","author":"Kontoghiorghe","year":"2014","journal-title":"World J. Methodol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e2020011","DOI":"10.4084\/mjhid.2020.011","article-title":"The History of Deferiprone (L1) and the Paradigm of the Complete Treatment of Iron Overload in Thalassaemia","volume":"12","author":"Kontoghiorghes","year":"2020","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J., Kolnagou, A., Demetriou, T., Neocleous, M., and Kontoghiorghe, C.N. (2021). New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115546"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1021\/mp500343j","article-title":"44Sc: An Attractive Isotope for Peptide-Based PET Imaging","volume":"11","author":"Hernandez","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.7150\/thno.20586","article-title":"Clinical translation and first in-human use of [44Sc]Sc-PSMA-617 for PET imaging of metastasized castrate-resistant prostate cancer","volume":"7","author":"Eppard","year":"2017","journal-title":"Theranostics"},{"key":"ref_158","first-page":"124","article-title":"First-in-Human PET\/CT imaging of metastatic neuroendocrine neoplasms with cyclotron-produced 44Sc-dotatoc: A proof-of-concept study","volume":"32","author":"Singh","year":"2017","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_159","first-page":"267","article-title":"Scandium-44 DOTATOC PET\/CT: First in-human molecular imaging of neuroendocrine tumors and possible perspectives for Theranostics","volume":"56","author":"Singh","year":"2015","journal-title":"J. Nucl. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s41181-016-0013-5","article-title":"44Sc for labeling of DOTA-and NODAGA-functionalized peptides: Preclinical in vitro and in vivo investigations","volume":"1","author":"Domnanich","year":"2017","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1021\/acs.molpharmaceut.1c00711","article-title":"Evaluation of 177Lu and 47Sc Picaga-Linked, Prostate-Specific Membrane Antigen-Targeting Constructs for Their Radiotherapeutic Efficacy and Dosimetry","volume":"18","author":"Vaughn","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1016\/j.apradiso.2012.08.004","article-title":"44Sc-DOTA- BN[2-14]NH2 in comparison to 68Ga-DOTA-BN[2-14]NH2 in pre-clinical investigation. Is 44Sc a potential radionuclide for PET?","volume":"70","author":"Koumarianou","year":"2012","journal-title":"Appl. Radiat. Isot."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/ajh.2830420403","article-title":"Selection of a new generation of orally active alpha-ketohydroxypyridine iron chelators intended for use in the treatment of iron overload","volume":"42","author":"Kontoghiorghes","year":"1993","journal-title":"Am. J. Hematol."},{"key":"ref_164","first-page":"65","article-title":"Oral iron chelation therapy with deferiprone. Monitoring of biochemical, drug and iron excretion changes","volume":"45","author":"Kontoghiorghes","year":"1995","journal-title":"Arzneimittelforschung"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1365-2141.1990.tb07887.x","article-title":"Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). I. Iron chelation and metabolic studies","volume":"76","author":"Kontoghiorghes","year":"1990","journal-title":"Br. J. Haematol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/03630260701726533","article-title":"Ethical issues and risk\/benefit assessment of iron chelation therapy: Advances with deferiprone\/deferoxamine combinations and concerns about the safety, efficacy and costs of deferasirox","volume":"32","author":"Kontoghiorghes","year":"2008","journal-title":"Hemoglobin"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J. (2023). Drug Selection and Posology, Optimal Therapies and Risk\/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316749"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0304-4165(86)90164-9","article-title":"Iron mobilisation from lactoferrin by chelators at physiological pH","volume":"882","author":"Kontoghiorghes","year":"1986","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Ianiro, G., Niro, A., Rosa, L., Valenti, P., Musci, G., and Cutone, A. (2023). To Boost or to Reset: The Role of Lactoferrin in Energy Metabolism. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115925"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"National Food Institute\u2014Technical University of Denmark, Doulgeridou, A., Amlund, H., Sloth, J.J., and Hansen, M. (2020). Review of Potentially Toxic Rare Earth Elements, Thallium and Tellurium in Plant-based Foods. EFSA J., 18, e181101.","DOI":"10.2903\/j.efsa.2020.e181101"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"14318","DOI":"10.1007\/s11356-020-08138-z","article-title":"Trend of the research on rare earth elements in environmental science","volume":"27","author":"Kang","year":"2020","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"de Vries-Huizing, D.M.V., Versleijen, M.W.J., Sinaasappel, M., Walraven, I., Geluk-Jonker, M.M., Tesselaar, M.E.T., Hendrikx, J.J.M.A., de Wit-van der Veen, B.J., and Stokkel, M.P.M. (2021). Haematotoxicity during peptide receptor radionuclide therapy: Baseline parameters differences and effect on patient\u2019s therapy course. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260073"},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"H\u00f6rmann, A.A., Klingler, M., Rangger, C., Mair, C., Decristoforo, C., Uprimny, C., Virgolini, I.J., and von Guggenberg, E. (2021). Radiopharmaceutical Formulation and Preclinical Testing of 68Ga-Labeled DOTA-MGS5 for the Regulatory Approval of a First Exploratory Clinical Trial. Pharmaceuticals, 14.","DOI":"10.3390\/ph14060575"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Imberti, C., Adumeau, P., Blower, J.E., Al Salemee, F., Bagu\u00f1a Torres, J., Lewis, J.S., Zeglis, B.M., Terry, S.Y.A., and Blower, P.J. (2020). Manipulating the In Vivo Behaviour of 68Ga with Tris(Hydroxypyridinone) Chelators: Pretargeting and Blood Clearance. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041496"},{"key":"ref_175","first-page":"173","article-title":"Interaction of L1, L1NAII and deferoxamine with gallium in vivo","volume":"28","author":"Eybl","year":"1992","journal-title":"Drugs Today"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Selyutina, O.Y., Babenko, S.V., Slepneva, I.A., Polyakov, N.E., and Kontoghiorghes, G.J. (2023). Increased Free Radical Generation during the Interaction of a Quinone-Quinoline Chelator with Metal Ions and the Enhancing Effect of Light. Pharmaceuticals, 16.","DOI":"10.3390\/ph16081116"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1749-6632.1990.tb24321.x","article-title":"Design, properties, and effective use of the oral chelator L1 and other alpha-ketohydroxypyridines in the treatment of transfusional iron overload in thalassemia","volume":"612","author":"Kontoghiorghes","year":"1990","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0020-1693(00)80369-2","article-title":"Comparative iron binding studies of bis and tris (3-hydroxy-2-methylpyrid-4-ones) and desferrioxamine","volume":"188","author":"Sheppard","year":"1991","journal-title":"Inorg. Chim. Acta"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J. (2022). New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213990"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/5954\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:24Z","timestamp":1760107824000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/5954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,29]]},"references-count":179,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["ijms25115954"],"URL":"https:\/\/doi.org\/10.3390\/ijms25115954","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,29]]}}}