Extended single-dose toxicity study of [211At]meta-astatobenzylguanidine in normal mice in preparation for the first-in-human clinical trial of targeted alpha therapy for pheochromocytoma and paraganglioma

Extended single-dose toxicity study of [211At]meta-astatobenzylguanidine in normal mice in preparation for the first-in-human clinical trial of targeted alpha therapy for pheochromocytoma and paraganglioma | 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 Extended single-dose toxicity study of [211At]meta-astatobenzylguanidine in normal mice in preparation for the first-in-human clinical trial of targeted alpha therapy for pheochromocytoma and paraganglioma Taiki Joho, Songji Zhao, Ken-Ichi Nishijima, Naoyuki Ukon, Saki Shimoyama, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6059261/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Jun, 2025 Read the published version in Annals of Nuclear Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Objective Targeted alpha-particle therapy (TAT) is promising with a greater therapeutic effect than conventional beta radionuclide therapy. To develop human clinical trials of [ 211 At] meta -astatobenzylguanidine ([ 211 At]MABG), we have conducted an extended single-dose toxicity study of [ 211 At]MABG in normal mice in consultation with the Pharmaceuticals and Medical Devices Agency (PMDA). We are currently working for human clinical trials of [ 211 At]MABG. After consultation with the Pharmaceuticals and Medical Devices Agency, we conducted a single-dose toxicity study of [ 211 At]MABG in normal mice in preparation for a human clinical trial of [ 211 At]MABG. Methods [ 211 At]MABG was manufactured at Fukushima Medical University, where doses of 16, 48, and 80 MBq/kg were administered to BALB/cCrSlc mice (90 males and 90 females, 9 weeks old). The mice were observed and weighed every day for 14 days after [ 211 At]MABG administration, as well as at any time between 14 and 35 days after [ 211 At]MABG administration. At the end of the observation period, necropsy, blood examination, organ weighing, and histopathological examinations were performed. Statistical analyses of body weight, blood test results, and organ weights were performed to compare the data between the control and treatment groups. Results In the 80-MBq/kg-administered group of females, two mice were emergently euthanized on day 8 because of the deterioration of their general condition. One mouse died spontaneously on day 9. Except for the two emergently euthanized mice and one mouse that died, both males and females showed volume-dependent deterioration in body weight, general condition, necropsy findings, blood test results, organ weights, and histopathological findings, but all except for genital organ weights showed a recovery trend after 35 days. Conclusions The extended single-dose toxicity study of [ 211 At]MABG conducted under the reliability criteria showed the toxicity of [ 211 At]MABG to hematopoietic cells, gastrointestinal mucosa, adrenal glands, and genital organs, especially at the dose of 80 MBq/kg. Under the conditions of this study, the approximate lethal dose of [ 211 At]MABG exceeds 80 MBq/kg, so the severely toxic dose in 10% of the animals was estimated to be 80 MBq/kg or greater. Astatine Clinical trial Mouse pheochromocytoma Toxicity study Full Text Cite Share Download PDF Status: Published Journal Publication published 18 Jun, 2025 Read the published version in Annals of Nuclear Medicine → Version 1 posted Reviewers agreed at journal 21 Apr, 2025 Reviewers invited by journal 21 Apr, 2025 Editor assigned by journal 15 Apr, 2025 First submitted to journal 14 Apr, 2025 You are reading this latest preprint version 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-6059261","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":445745590,"identity":"97a8a4a0-b0ac-4474-99ee-dd4a03c69742","order_by":0,"name":"Taiki 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To develop human clinical trials of [\u003csup\u003e211\u003c/sup\u003eAt]\u003cem\u003emeta\u003c/em\u003e-astatobenzylguanidine ([\u003csup\u003e211\u003c/sup\u003eAt]MABG), we have conducted an extended single-dose toxicity study of [\u003csup\u003e211\u003c/sup\u003eAt]MABG in normal mice in consultation with the Pharmaceuticals and Medical Devices Agency (PMDA). We are currently working for human clinical trials of [\u003csup\u003e211\u003c/sup\u003eAt]MABG. After consultation with the Pharmaceuticals and Medical Devices Agency, we conducted a single-dose toxicity study of [\u003csup\u003e211\u003c/sup\u003eAt]MABG in normal mice in preparation for a human clinical trial of [\u003csup\u003e211\u003c/sup\u003eAt]MABG.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e[\u003csup\u003e211\u003c/sup\u003eAt]MABG was manufactured at Fukushima Medical University, where doses of 16, 48, and 80 MBq/kg were administered to BALB/cCrSlc mice (90 males and 90 females, 9 weeks old). The mice were observed and weighed every day for 14 days after [\u003csup\u003e211\u003c/sup\u003eAt]MABG administration, as well as at any time between 14 and 35 days after [\u003csup\u003e211\u003c/sup\u003eAt]MABG administration. At the end of the observation period, necropsy, blood examination, organ weighing, and histopathological examinations were performed. Statistical analyses of body weight, blood test results, and organ weights were performed to compare the data between the control and treatment groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn the 80-MBq/kg-administered group of females, two mice were emergently euthanized on day 8 because of the deterioration of their general condition. One mouse died spontaneously on day 9. Except for the two emergently euthanized mice and one mouse that died, both males and females showed volume-dependent deterioration in body weight, general condition, necropsy findings, blood test results, organ weights, and histopathological findings, but all except for genital organ weights showed a recovery trend after 35 days.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe extended single-dose toxicity study of [\u003csup\u003e211\u003c/sup\u003eAt]MABG conducted under the reliability criteria showed the toxicity of [\u003csup\u003e211\u003c/sup\u003eAt]MABG to hematopoietic cells, gastrointestinal mucosa, adrenal glands, and genital organs, especially at the dose of 80 MBq/kg. Under the conditions of this study, the approximate lethal dose of [\u003csup\u003e211\u003c/sup\u003eAt]MABG exceeds 80 MBq/kg, so the severely toxic dose in 10% of the animals was estimated to be 80 MBq/kg or greater.\u003c/p\u003e","manuscriptTitle":"Extended single-dose toxicity study of [211At]meta-astatobenzylguanidine in normal mice in preparation for the first-in-human clinical trial of targeted alpha therapy for pheochromocytoma and paraganglioma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-24 20:11:45","doi":"10.21203/rs.3.rs-6059261/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-04-21T12:17:02+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-21T12:09:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-15T06:21:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Nuclear Medicine","date":"2025-04-15T01:32:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-nuclear-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anme","sideBox":"Learn more about [Annals of Nuclear Medicine](http://link.springer.com/journal/12149)","snPcode":"12149","submissionUrl":"https://www.editorialmanager.com/anme/default2.aspx","title":"Annals of Nuclear Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5a1fbf69-5041-49ec-9276-7e37b5b9f848","owner":[],"postedDate":"April 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-23T16:00:19+00:00","versionOfRecord":{"articleIdentity":"rs-6059261","link":"https://doi.org/10.1007/s12149-025-02065-0","journal":{"identity":"annals-of-nuclear-medicine","isVorOnly":false,"title":"Annals of Nuclear Medicine"},"publishedOn":"2025-06-18 15:57:20","publishedOnDateReadable":"June 18th, 2025"},"versionCreatedAt":"2025-04-24 20:11:45","video":"","vorDoi":"10.1007/s12149-025-02065-0","vorDoiUrl":"https://doi.org/10.1007/s12149-025-02065-0","workflowStages":[]},"version":"v1","identity":"rs-6059261","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6059261","identity":"rs-6059261","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}