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      Natural and enriched Cr target development for production of Manganese-52

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          Abstract

          52Mn is a promising PET radiometal with a half-life of 5.6 days and an average positron energy of 242 keV. Typically, chromium of natural isotope abundance is used as a target material to produce this isotope through the nat/52Cr(p,n) 52Mn reaction. While natural Cr is a suitable target material, higher purity 52Mn could be produced by transitioning to enriched 52Cr targets to prevent the co-production of long-lived 54Mn (t 1/2 = 312 day). Unfortunately, 52Cr targets are not cost-effective without recycling processes in place, therefore, this work aims to explore routes to prepare Cr targets that could be recycled. Natural Cr foils, metal powder pellets, enriched chromium-52 oxide and Cr(III) electroplated targets were investigated in this work. Each of these cyclotron targets were irradiated, and the produced 52Mn was purified, when possible, using a semi-automated system. An improved purification by solid-phase anion exchange from ethanol-HCl mixtures resulted in recoveries of 94.5 ± 2.2% of 52Mn. The most promising target configuration to produce a recyclable target was electroplated Cr(III). This work presents several pathways to optimize enriched Cr targets for the production of high purity 52Mn.

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          SRIM – The stopping and range of ions in matter (2010)

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            52Mn Production for PET/MRI Tracking Of Human Stem Cells Expressing Divalent Metal Transporter 1 (DMT1)

            There is a growing demand for long-term in vivo stem cell imaging for assessing cell therapy techniques and guiding therapeutic decisions. This work develops the production of 52Mn and establishes proof of concept for the use of divalent metal transporter 1 (DMT1) as a positron emission tomography (PET) and magnetic resonance imaging (MRI) reporter gene for stem cell tracking in the rat brain. 52Mn was produced via proton irradiation of a natural chromium target. In a comparison of two 52Mn separation methods, solvent-solvent extraction was preferred over ion exchange chromatography because of reduced chromium impurities and higher 52Mn recovery. In vitro uptake of Mn-based PET and MRI contrast agents (52Mn2+ and Mn2+, respectively) was enhanced in DMT1 over-expressing human neural progenitor cells (hNPC-DMT1) compared to wild-type control cells (hNPC-WT). After cell transplantation in the rat striatum, increased uptake of Mn-based contrast agents in grafted hNPC-DMT1 was detected in in vivo manganese-enhanced MRI (MEMRI) and ex vivo PET and autoradiography. These initial studies indicate that this approach holds promise for dual-modality PET/MR tracking of transplanted stem cells in the central nervous system and prompt further investigation into the clinical applicability of this technique.
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              Novel Preparation Methods of 52Mn for ImmunoPET Imaging

              52 Mn ( t 1/2 = 5.59 d, β + = 29.6%, E β ave = 0.24 MeV) shows promise in positron emission tomography (PET) and in dual-modality manganese-enhanced magnetic resonance imaging (MEMRI) applications including neural tractography, stem cell tracking, and biological toxicity studies. The extension to bioconjugate application requires high-specific-activity 52 Mn in a state suitable for macromolecule labeling. To that end a 52 Mn production, purification, and labeling system is presented, and its applicability in preclinical, macromolecule PET is shown using the conjugate 52 Mn-DOTA-TRC105. 52 Mn is produced by 60 μ A, 16 MeV proton irradiation of natural chromium metal pressed into a silver disc support. Radiochemical separation proceeds by strong anion exchange chromatography of the dissolved Cr target, employing a semiorganic mobile phase, 97:3 (v:v) ethanol:HCl (11 M, aqueous). The method is 62 ± 14% efficient ( n = 7) in 52 Mn recovery, leading to a separation factor from Cr of (1.6 ± 1.0) × 10 6 ( n = 4), and an average effective specific activity of 0.8 GBq/ μ mol ( n = 4) in titration against DOTA. 52 Mn-DOTA-TRC105 conjugation and labeling demonstrate the potential for chelation applications. In vivo images acquired using PET/CT in mice bearing 4T1 xenograft tumors are presented. Peak tumor uptake is 18.7 ± 2.7%ID/g at 24 h post injection and ex vivo 52 Mn biodistribution validates the in vivo PET data. Free 52 Mn 2+ (as chloride or acetate) is used as a control in additional mice to evaluate the nontargeted biodistribution in the tumor model.
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                Author and article information

                Contributors
                lapi@uab.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                20 January 2023
                20 January 2023
                2023
                : 13
                : 1167
                Affiliations
                [1 ]GRID grid.265892.2, ISNI 0000000106344187, Department of Radiology, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [2 ]GRID grid.265892.2, ISNI 0000000106344187, Department of Chemistry, , University of Alabama at Birmingham, ; Birmingham, Al USA
                Article
                27257
                10.1038/s41598-022-27257-w
                9859786
                36670119
                1013efc5-bcbb-4f95-9d5c-e9cbb92bdc4e
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 October 2022
                : 28 December 2022
                Categories
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                © The Author(s) 2023

                Uncategorized
                chemistry,inorganic chemistry,nuclear chemistry
                Uncategorized
                chemistry, inorganic chemistry, nuclear chemistry

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