Automated, cassette-based isolation and formulation of high-purity [61Cu]CuCl2 from solid Ni targets

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Abstract Background: A need for improved, cassette-based automation of 61Cu separation from irradiated Ni targets was identified given the growing interest in theranostics and generally lengthy separation chemistries for 64Cu/64Ni, upon which 61Cu chemistry is often based. Methods: A method for separating 61Cu from irradiated natNi targets was therefore developed, with provision for target recycling. Following deuteron irradiation, electroplated natNi targets were remotely transferred from the cyclotron and dissolved in acid. The dissolved target solution was then transferred to an automated FASTlab chemistry module, where sequential TBP and TK201 (Triskem) resins isolated the [61Cu]CuCl2, removed Ni, Co, and Fe, and concentrated the product into a formulation suitable for anticipated radiolabelling reactions. Results: 61Cu saturation yields of 190 ± 33 MBq/µA from energetically thick natNi targets were measured. The average, decay-corrected, activity-based dissolution efficiency was 97.5 ± 1.4 % with an average radiochemical yield of 90.4 ± 3.2 % (N = 5). The isolated activity was collected approximately 65 minutes post end of bombardment in ~2 mL of 0.06 M HCl (HCl concentration was verified by titration). Quality control of the isolated [61Cu]CuCl2 (N = 5) measured 58Co content of (8.3 ± 0.6) × 10-5 % vs. 61Cu by activity, Ni separation factors ≥ (2.2 ± 1.8) × 106, EoB molar activities 85 ± 23 GBq/µmol and NOTA-based EoB apparent molar activities of 31 ± 8 MBq/nmol and 201 MBq/nmol for the 30 min and 3.3 h (N = 1) irradiations, respectively. Conclusion: High purity 61Cu was produced with the developed automated method using a single-use, cassette-based approach. It was also applicable for 64Cu, as demonstrated with a single proof-of-concept 64Ni target production run.
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Automated, cassette-based isolation and formulation of high-purity [61Cu]CuCl2 from solid Ni targets | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Automated, cassette-based isolation and formulation of high-purity [ 61 Cu]CuCl 2 from solid Ni targets Johan Svedjehed, Christopher J Kutyreff, Jonathan W Engle, Katherine Gagnon This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-41194/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Nov, 2020 Read the published version in EJNMMI Radiopharmacy and Chemistry → Version 2 posted 4 You are reading this latest preprint version Show more versions Abstract Background: A need for improved, cassette-based automation of 61 Cu separation from irradiated Ni targets was identified given the growing interest in theranostics and generally lengthy separation chemistries for 64 Cu/ 64 Ni, upon which 61 Cu chemistry is often based. Methods: A method for separating 61 Cu from irradiated nat Ni targets was therefore developed, with provision for target recycling. Following deuteron irradiation, electroplated nat Ni targets were remotely transferred from the cyclotron and dissolved in acid. The dissolved target solution was then transferred to an automated FASTlab chemistry module, where sequential TBP and TK201 (Triskem) resins isolated the [ 61 Cu]CuCl 2 , removed Ni, Co, and Fe, and concentrated the product into a formulation suitable for anticipated radiolabelling reactions. Results: 61 Cu saturation yields of 190 ± 33 MBq/µA from energetically thick nat Ni targets were measured. The average, decay-corrected, activity-based dissolution efficiency was 97.5 ± 1.4 % with an average radiochemical yield of 90.4 ± 3.2 % (N = 5). The isolated activity was collected approximately 65 minutes post end of bombardment in ~2 mL of 0.06 M HCl (HCl concentration was verified by titration). Quality control of the isolated [ 61 Cu]CuCl 2 (N = 5) measured 58 Co content of (8.3 ± 0.6) × 10 -5 % vs. 61 Cu by activity, Ni separation factors ≥ (2.2 ± 1.8) × 10 6 , EoB molar activities 85 ± 23 GBq/µmol and NOTA-based EoB apparent molar activities of 31 ± 8 MBq/nmol and 201 MBq/nmol for the 30 min and 3.3 h (N = 1) irradiations, respectively. Conclusion: High purity 61 Cu was produced with the developed automated method using a single-use, cassette-based approach. It was also applicable for 64 Cu, as demonstrated with a single proof-of-concept 64 Ni target production run. Health Policy 61Cu (radiocopper) Automation/automated Solid target Dissolution Recycling Figures Figure 1 Figure 2 Full Text Cite Share Download PDF Status: Published Journal Publication published 05 Nov, 2020 Read the published version in EJNMMI Radiopharmacy and Chemistry → Version 2 posted Editorial decision: Accept 30 Sep, 2020 Editor assigned by journal 29 Sep, 2020 Submission checks completed at journal 28 Sep, 2020 Editor invited by journal 28 Sep, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-41194","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":2959151,"identity":"4b8603c5-2759-40f7-bb8e-3bc3ea66cbf6","order_by":0,"name":"Johan Svedjehed","email":"","orcid":"","institution":"GE Healthcare","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Johan","middleName":"","lastName":"Svedjehed","suffix":""},{"id":2959152,"identity":"4eaf4ccf-32be-46db-a265-84441a084bc6","order_by":1,"name":"Christopher J Kutyreff","email":"","orcid":"","institution":"University of Wisconsin Madison School of Medicine and Public Health","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Christopher","middleName":"J","lastName":"Kutyreff","suffix":""},{"id":2959153,"identity":"5e2afdaf-6c48-498c-b991-79bafcbb12fd","order_by":2,"name":"Jonathan W Engle","email":"","orcid":"","institution":"University of Wisconsin Madison School of Medicine and Public Health","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jonathan","middleName":"W","lastName":"Engle","suffix":""},{"id":2959154,"identity":"e73d5754-a854-45ea-ad68-2d19965625db","order_by":3,"name":"Katherine Gagnon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYBACCQYGNggFA/yEtTCjaZFsIE4LEjA4QECLZPv5Yw8+7rHI42dgv/jx6w6bPOPziw8w/KjYhlOLNE8yu+GMZxLFkg08xdKyZ9KKzW48S2DsOXMbpxY5hmQ2aZ4DEokbDvAkSEu2HU7cduOMATNjGx4t/I/ZpP8Atew/wJP8G6Rl84zzH/BqkZYA2sIAsoWB/ZjkR6CWDfw9DHi1SM54bCbZA9Qy4zAPmzVjW1rijBtsBgfx+UXifOIziR8H6hL729sf3/zZZpPY33/44YMfFbi1IAAzjwEzD9iUBIYDRKgHAfYHjD9AND+xGkbBKBgFo2CkAACnBFkhQBL/7wAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-6513-8738","institution":"GE Healthcare","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Katherine","middleName":"","lastName":"Gagnon","suffix":""}],"badges":[],"createdAt":"2020-07-11 18:28:52","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-41194/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-41194/v2","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s41181-020-00108-7","type":"published","date":"2020-11-05T15:02:35+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":2839499,"identity":"f71b1a04-4f5e-4c9f-8aac-e98b6b946b66","added_by":"auto","created_at":"2020-10-07 19:18:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":136246,"visible":true,"origin":"","legend":"Two-column approach for 61Cu separation. 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Following deuteron irradiation, electroplated \u003csup\u003enat\u003c/sup\u003eNi targets were remotely transferred from the cyclotron and dissolved in acid. The dissolved target solution was then transferred to an automated FASTlab chemistry module, where sequential TBP and TK201 (Triskem) resins isolated the [\u003csup\u003e61\u003c/sup\u003eCu]CuCl\u003csub\u003e2\u003c/sub\u003e, removed Ni, Co, and Fe, and concentrated the product into a formulation suitable for anticipated radiolabelling reactions. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003e\u003csup\u003e61\u003c/sup\u003eCu saturation yields of 190 ± 33 MBq/µA from energetically thick \u003csup\u003enat\u003c/sup\u003eNi targets were measured. The average, decay-corrected, activity-based dissolution efficiency was 97.5 ± 1.4 % with an average radiochemical yield of 90.4 ± 3.2 % (N = 5). The isolated activity was collected approximately 65 minutes post end of bombardment in ~2 mL of 0.06 M HCl (HCl concentration was verified by titration). Quality control of the isolated [\u003csup\u003e61\u003c/sup\u003eCu]CuCl\u003csub\u003e2\u003c/sub\u003e (N = 5) measured \u003csup\u003e58\u003c/sup\u003eCo content of (8.3 ± 0.6) × 10\u003csup\u003e-5\u003c/sup\u003e % vs. \u003csup\u003e61\u003c/sup\u003eCu by activity, Ni separation factors ≥ (2.2 ± 1.8) × 10\u003csup\u003e6\u003c/sup\u003e, EoB molar activities 85 ± 23 GBq/µmol and NOTA-based EoB apparent molar activities of 31 ± 8 MBq/nmol and 201 MBq/nmol for the 30 min and 3.3 h (N = 1) irradiations, respectively. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003cem\u003e \u003c/em\u003eHigh purity \u003csup\u003e61\u003c/sup\u003eCu was produced with the developed automated method using a single-use, cassette-based approach. It was also applicable for \u003csup\u003e64\u003c/sup\u003eCu, as demonstrated with a single proof-of-concept \u003csup\u003e64\u003c/sup\u003eNi target production run.\u003c/p\u003e","manuscriptTitle":"Automated, cassette-based isolation and formulation of high-purity [61Cu]CuCl2\u0026nbsp;from solid Ni targets","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2020-10-07 19:18:01","doi":"10.21203/rs.3.rs-41194/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2020-09-30T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-09-29T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-09-28T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-09-28T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"ejnmmi-radiopharmacy-and-chemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"erpc","sideBox":"Learn more about [EJNMMI Radiopharmacy and Chemistry](http://ejnmmipharmchem.springeropen.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/erpc/default.aspx","title":"EJNMMI Radiopharmacy and Chemistry","twitterHandle":"@officialEANM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-07-15 17:03:46","doi":"10.21203/rs.3.rs-41194/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2020-08-24T12:00:00+00:00","index":2,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"decision","content":"Minor revision","date":"2020-08-24T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-08-01T12:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"reviewerAgreed","content":"","date":"2020-07-23T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-07-19T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-07-16T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-07-15T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-07-14T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-07-11T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-07-08T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"ejnmmi-radiopharmacy-and-chemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"erpc","sideBox":"Learn more about [EJNMMI Radiopharmacy and Chemistry](http://ejnmmipharmchem.springeropen.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/erpc/default.aspx","title":"EJNMMI Radiopharmacy and Chemistry","twitterHandle":"@officialEANM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"99d8be69-660f-4530-8039-51f394e9ddb7","owner":[],"postedDate":"October 7th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":719855,"name":"Health Policy"}],"tags":[],"updatedAt":"2020-11-08T15:03:18+00:00","versionOfRecord":{"articleIdentity":"rs-41194","link":"https://doi.org/10.1186/s41181-020-00108-7","journal":{"identity":"ejnmmi-radiopharmacy-and-chemistry","isVorOnly":false,"title":"EJNMMI Radiopharmacy and Chemistry"},"publishedOn":"2020-11-05 15:02:35","publishedOnDateReadable":"November 5th, 2020"},"versionCreatedAt":"2020-10-07 19:18:01","video":"","vorDoi":"10.1186/s41181-020-00108-7","vorDoiUrl":"https://doi.org/10.1186/s41181-020-00108-7","workflowStages":[]},"version":"v2","identity":"rs-41194","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-41194","identity":"rs-41194","version":["v2"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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