James M. Omweri , Volkan Tekin , Shefali Saini , Hailey A. Houson , Samith B. Jayawardana , Daniel A. Decato , Gayan B. Wijeratne , Suzanne E. Lapi
{"title":"用于 PET 成像应用的锰-52 螯合化学","authors":"James M. Omweri , Volkan Tekin , Shefali Saini , Hailey A. Houson , Samith B. Jayawardana , Daniel A. Decato , Gayan B. Wijeratne , Suzanne E. Lapi","doi":"10.1016/j.nucmedbio.2023.108874","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Due to its decay and chemical properties, interest in manganese-52 has increased for development of long-lived PET radiopharmaceuticals. Its long half-life of 5.6 days, low average positron energy (242 keV), and sufficient positron decay branching ratio make it suitable for radiolabeling macromolecules for investigating slow biological processes. This work aims to establish suitable chelators for manganese-52 that can be radiolabeled at mild conditions through the evaluation of commercially available chelators.</p></div><div><h3>Methods</h3><p>Manganese-52 was produced through the nuclear reaction <sup>Nat</sup>Cr(p,n)<sup>52</sup>Mn by irradiation of natural chromium targets on a TR24 cyclotron followed by purification through ion exchange chromatography. The radiolabeling efficiencies of chelators: DOTA, DiAmsar, TETA, DO3A, NOTA, 4′-Formylbenzo-15-crown-5, Oxo-DO3A, and DFO, were assessed by investigating the impact of pH, buffer type, and temperature. <em>In vitro</em> stability of [<sup>52</sup>Mn]Mn(DO3A)<sup>−</sup>, [<sup>52</sup>Mn]Mn(Oxo-DO3A)<sup>−</sup>, and [<sup>52</sup>Mn]Mn(DOTA)<sup>2−</sup> were evaluated in mouse serum. The radiocomplexes were also evaluated <em>in vivo</em> in mice. Crystals of [Mn(Oxo-DO3A)]<sup>−</sup> were synthesized by reacting Oxo-DO3A with MnCl<sub>2</sub> and characterized by single crystal X-ray diffraction.</p></div><div><h3>Results</h3><p>Yields of 185 ± 19 MBq (5.0 ± 0.5 mCi) (n = 4) of manganese-52 were produced at the end of a 4 h, 15 μA, bombardment with 12.5 MeV protons. NOTA, DO3A, DOTA, and Oxo-DO3A chelators were readily radiolabeled with >96 % radiochemical purity at all conditions. Manganese radiocomplexes of Oxo-DO3A, DOTA, and DO3A remained stable <em>in vitro</em> up to 5 days and exhibited different biodistribution profiles compared to [<sup>52</sup>Mn]MnCl<sub>2</sub>. The solid-state structure of Mn-Oxo-DO3A complex was determined by single-crystal X-ray diffraction.</p></div><div><h3>Conclusions</h3><p>DO3A and Oxo-DO3A are suitable chelators for manganese-52 which are readily radiolabeled at mild conditions with high molar activity, and demonstrate both <em>in vitro</em> and <em>in vivo</em> stability.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108874"},"PeriodicalIF":3.6000,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805123006029/pdfft?md5=03b22d19bd51af10dd7051d5419ab246&pid=1-s2.0-S0969805123006029-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Chelation chemistry of manganese-52 for PET imaging applications\",\"authors\":\"James M. Omweri , Volkan Tekin , Shefali Saini , Hailey A. Houson , Samith B. Jayawardana , Daniel A. Decato , Gayan B. Wijeratne , Suzanne E. Lapi\",\"doi\":\"10.1016/j.nucmedbio.2023.108874\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Due to its decay and chemical properties, interest in manganese-52 has increased for development of long-lived PET radiopharmaceuticals. Its long half-life of 5.6 days, low average positron energy (242 keV), and sufficient positron decay branching ratio make it suitable for radiolabeling macromolecules for investigating slow biological processes. This work aims to establish suitable chelators for manganese-52 that can be radiolabeled at mild conditions through the evaluation of commercially available chelators.</p></div><div><h3>Methods</h3><p>Manganese-52 was produced through the nuclear reaction <sup>Nat</sup>Cr(p,n)<sup>52</sup>Mn by irradiation of natural chromium targets on a TR24 cyclotron followed by purification through ion exchange chromatography. The radiolabeling efficiencies of chelators: DOTA, DiAmsar, TETA, DO3A, NOTA, 4′-Formylbenzo-15-crown-5, Oxo-DO3A, and DFO, were assessed by investigating the impact of pH, buffer type, and temperature. <em>In vitro</em> stability of [<sup>52</sup>Mn]Mn(DO3A)<sup>−</sup>, [<sup>52</sup>Mn]Mn(Oxo-DO3A)<sup>−</sup>, and [<sup>52</sup>Mn]Mn(DOTA)<sup>2−</sup> were evaluated in mouse serum. The radiocomplexes were also evaluated <em>in vivo</em> in mice. Crystals of [Mn(Oxo-DO3A)]<sup>−</sup> were synthesized by reacting Oxo-DO3A with MnCl<sub>2</sub> and characterized by single crystal X-ray diffraction.</p></div><div><h3>Results</h3><p>Yields of 185 ± 19 MBq (5.0 ± 0.5 mCi) (n = 4) of manganese-52 were produced at the end of a 4 h, 15 μA, bombardment with 12.5 MeV protons. NOTA, DO3A, DOTA, and Oxo-DO3A chelators were readily radiolabeled with >96 % radiochemical purity at all conditions. Manganese radiocomplexes of Oxo-DO3A, DOTA, and DO3A remained stable <em>in vitro</em> up to 5 days and exhibited different biodistribution profiles compared to [<sup>52</sup>Mn]MnCl<sub>2</sub>. The solid-state structure of Mn-Oxo-DO3A complex was determined by single-crystal X-ray diffraction.</p></div><div><h3>Conclusions</h3><p>DO3A and Oxo-DO3A are suitable chelators for manganese-52 which are readily radiolabeled at mild conditions with high molar activity, and demonstrate both <em>in vitro</em> and <em>in vivo</em> stability.</p></div>\",\"PeriodicalId\":19363,\"journal\":{\"name\":\"Nuclear medicine and biology\",\"volume\":\"128 \",\"pages\":\"Article 108874\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2023-12-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0969805123006029/pdfft?md5=03b22d19bd51af10dd7051d5419ab246&pid=1-s2.0-S0969805123006029-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nuclear medicine and biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0969805123006029\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nuclear medicine and biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969805123006029","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Chelation chemistry of manganese-52 for PET imaging applications
Introduction
Due to its decay and chemical properties, interest in manganese-52 has increased for development of long-lived PET radiopharmaceuticals. Its long half-life of 5.6 days, low average positron energy (242 keV), and sufficient positron decay branching ratio make it suitable for radiolabeling macromolecules for investigating slow biological processes. This work aims to establish suitable chelators for manganese-52 that can be radiolabeled at mild conditions through the evaluation of commercially available chelators.
Methods
Manganese-52 was produced through the nuclear reaction NatCr(p,n)52Mn by irradiation of natural chromium targets on a TR24 cyclotron followed by purification through ion exchange chromatography. The radiolabeling efficiencies of chelators: DOTA, DiAmsar, TETA, DO3A, NOTA, 4′-Formylbenzo-15-crown-5, Oxo-DO3A, and DFO, were assessed by investigating the impact of pH, buffer type, and temperature. In vitro stability of [52Mn]Mn(DO3A)−, [52Mn]Mn(Oxo-DO3A)−, and [52Mn]Mn(DOTA)2− were evaluated in mouse serum. The radiocomplexes were also evaluated in vivo in mice. Crystals of [Mn(Oxo-DO3A)]− were synthesized by reacting Oxo-DO3A with MnCl2 and characterized by single crystal X-ray diffraction.
Results
Yields of 185 ± 19 MBq (5.0 ± 0.5 mCi) (n = 4) of manganese-52 were produced at the end of a 4 h, 15 μA, bombardment with 12.5 MeV protons. NOTA, DO3A, DOTA, and Oxo-DO3A chelators were readily radiolabeled with >96 % radiochemical purity at all conditions. Manganese radiocomplexes of Oxo-DO3A, DOTA, and DO3A remained stable in vitro up to 5 days and exhibited different biodistribution profiles compared to [52Mn]MnCl2. The solid-state structure of Mn-Oxo-DO3A complex was determined by single-crystal X-ray diffraction.
Conclusions
DO3A and Oxo-DO3A are suitable chelators for manganese-52 which are readily radiolabeled at mild conditions with high molar activity, and demonstrate both in vitro and in vivo stability.
期刊介绍：
Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized.
These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field.
Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.
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