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      Optimization of Cation Exchange for the Separation of Actinium-225 from Radioactive Thorium, Radium-223 and Other Metals

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          Abstract

          Actinium-225 ( 225Ac) can be produced with a linear accelerator by proton irradiation of a thorium (Th) target, but the Th also underdoes fission and produces 400 other radioisotopes. No research exists on optimization of the cation step for the purification. The research herein examines the optimization of the cation exchange step for the purification of 225Ac. The following variables were tested: pH of load solution (1.5–4.6); rinse steps with various concentrations of HCl, HNO 3, H 2SO 4, and combinations of HCl and HNO 3; various thorium chelators to block retention; MP50 and AG50 resins; and retention of 20–45 elements with different rinse sequences. The research indicated that HCl removes more isotopes earlier than HNO 3, but that some elements, such as barium and radium, could be eluted with ≥2.5 M HNO 3. The optimal pH of the load solution was 1.5–2.0, and the optimized rinse sequence was five bed volumes (BV) of 1 M citric acid pH 2.0, 3 BV of water, 3 BV of 2 M HNO 3, 6 BV of 2.5 M HNO 3 and 20 BV of 6 M HNO 3. The sequence recovered >90% of 225Ac with minimal 223Ra and thorium present.

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          213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

          Purpose Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as 90Y/177Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with 213Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Methods Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with 90Y/177Lu-DOTATOC were treated with an intraarterial infusion of 213Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of 213Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and 68Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. Results The biodistribution of 213Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. Conclusion TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. Electronic supplementary material The online version of this article (doi:10.1007/s00259-014-2857-9) contains supplementary material, which is available to authorized users.
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            An Eighteen-Membered Macrocyclic Ligand for Actinium-225 Targeted Alpha Therapy

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              Bismuth-213 and actinium-225 -- generator performance and evolving therapeutic applications of two generator-derived alpha-emitting radioisotopes.

              The alpha emitters (225)Ac and (213)Bi are promising therapeutic radionuclides for application in targeted alpha therapy of cancer and infectious diseases. Both alpha emitters are available with high specific activity from established radionuclide generators. Their favourable chemical and physical properties have led to the conduction of a large number of preclinical studies and several clinical trials, demonstrating the feasibility, safety and therapeutic efficacy of targeted alpha therapy with (225)Ac and (213)Bi. This review describes methods for the production of (225)Ac and (213)Bi and gives an overview of (225)Ac/(213)Bi radionuclide generator systems. Selected preclinical studies are highlighted and the current clinical experience with (225)Ac and (213)Bi is summarized.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                18 May 2019
                May 2019
                : 24
                : 10
                : 1921
                Affiliations
                [1 ]Isotope Production Laboratory, Collider-Accelerator Division, Brookhaven National Laboratory, Upton, NY 11973, USA; ccutler@ 123456bnl.gov (C.S.C.); lmausner@ 123456bnl.gov (L.M.); dmedvede@ 123456bnl.gov (D.M.)
                [2 ]Department of Biology, Chemistry, and Geoscience, Fairmont State University, Fairmont, WV 26554, USA; bfoley@ 123456tamu.edu
                [3 ]Department of Chemistry, University at Buffalo, the State University of New York, Buffalo, NY 14260, USA; brynator@ 123456buffalo.edu
                [4 ]Department of Chemistry, Elizabeth City State University, Elizabeth City, NC 27909, USA; mmwilken412@ 123456students.ecsu.edu
                Author notes
                [* ]Correspondence: jfitzsimmons@ 123456bnl.gov ; Tel.: +1-631-344-4453
                [†]

                These authors contributed equally to this work.

                [‡]

                Present affiliation: Bryna Torre at University of Buffalo School of Medicine, Bryan Foley at Texas A&M University, 400 Bizzell St, College Station, TX 77843, USA.

                Author information
                https://orcid.org/0000-0001-9892-1534
                https://orcid.org/0000-0003-0570-769X
                Article
                molecules-24-01921
                10.3390/molecules24101921
                6571705
                31109077
                c2748133-629a-4f29-85b2-f78e0bcf8255
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 March 2019
                : 16 May 2019
                Categories
                Article

                lanthanum,rhodium,ag50,mp50,fission products,actinium-225,225ac,223ra,227th,thorium

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