Synthesis and Preclinical Evaluation of Novel 68Ga-Labeled Bispecific SSTR/GLP-1R Targeting Probes for Neuroendocrine Neoplasms Imaging

Synthesis and Preclinical Evaluation of Novel 68Ga-Labeled Bispecific SSTR/GLP-1R Targeting Probes for Neuroendocrine Neoplasms Imaging | 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 Synthesis and Preclinical Evaluation of Novel 68Ga-Labeled Bispecific SSTR/GLP-1R Targeting Probes for Neuroendocrine Neoplasms Imaging Chuyin Ruan, Xiaoqiang Yang, Yongshuai Qi, Xiaohua Chi, Guiping Li, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4317886/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The neuroendocrine neoplasms (NENs) have a poor early diagnostic rate. To increase the detection rate of NENs, this project aims to build a PET probe, DOTA-exendin-4-TOC, that targets both SSTR and GLP-1R. Procedures The novel dual-target molecular probe DOTA-exendin-4-TOC was constructed, and radiolabeled with gallium-68 to target both SSTR and GLP-1R. In vivo and in vitro stability tests, cellular uptake tests, biodistribution, and microPET/CT studies were used to examine the PET probe properties in the tumor models including RIN-M5F, INS-1, and AR42J. Results The synthesis of [ 68 Ga]Ga-DOTA-exendin-4-TOC had a radiochemical purity of more than 95%. The radiolabel demonstrated better stability both in vivo (in mouse serum) and in vitro (in PBS), and it is eliminated by the urine system. RIN-M5F cells, INS-1 cells, and AR42J cells were found to have an uptake effect on [ 68 Ga]Ga-DOTA-exendin-4-TOC in vitro cell uptake experiments. The tumor models containing RIN-M5F, INS-1, and AR42J demonstrated uptake of [ 68 Ga]Ga-DOTA-exendin-4-TOC at 60 and 120 minutes, according to microPET/CT imaging. Higher values of tumor uptake were noted for AR42J at 1.50 ± 0.10 (120 min), INS-1 at 1.57 ± 0.12 (60 min), and RIN-M5F at 0.87 ± 0.11 (60 min). All three tumor models exhibited tumor tissues' uptake of [ 68 Ga]Ga-DOTA-exendin-4-TOC, according to in vivo metabolism studies. Furthermore, the kidneys had the highest distribution of radioactivity. Conclusions In this work, a new molecular probe that targets SSTR and GLP-1R was successfully constructed and radiolabeled with [ 68 Ga]Ga, called [ 68 Ga]Ga-DOTA-exendin-4-TOC. This novel dual-target probe could be applied as a valuable tool for improving the detection rate in patients in the future. Neuroendocrine neoplasms Dual-target molecular probe micro-PET imaging [68Ga]Ga-DOTA-exendin-4-TOC Full Text Cite Share Download PDF Status: Posted Version 1 posted 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-4317886","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":304653077,"identity":"6fae17d1-b7d1-4d9c-96a1-684f7c7163f4","order_by":0,"name":"Chuyin 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Imaging","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Neuroendocrine neoplasms, Dual-target molecular probe, micro-PET imaging, [68Ga]Ga-DOTA-exendin-4-TOC","lastPublishedDoi":"10.21203/rs.3.rs-4317886/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4317886/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe neuroendocrine neoplasms (NENs) have a poor early diagnostic rate. To increase the detection rate of NENs, this project aims to build a PET probe, DOTA-exendin-4-TOC, that targets both SSTR and GLP-1R.\u003c/p\u003e\u003ch2\u003eProcedures\u003c/h2\u003e \u003cp\u003eThe novel dual-target molecular probe DOTA-exendin-4-TOC was constructed, and radiolabeled with gallium-68 to target both SSTR and GLP-1R. In vivo and in vitro stability tests, cellular uptake tests, biodistribution, and microPET/CT studies were used to examine the PET probe properties in the tumor models including RIN-M5F, INS-1, and AR42J.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe synthesis of [\u003csup\u003e68\u003c/sup\u003eGa]Ga-DOTA-exendin-4-TOC had a radiochemical purity of more than 95%. The radiolabel demonstrated better stability both in vivo (in mouse serum) and in vitro (in PBS), and it is eliminated by the urine system. RIN-M5F cells, INS-1 cells, and AR42J cells were found to have an uptake effect on [\u003csup\u003e68\u003c/sup\u003eGa]Ga-DOTA-exendin-4-TOC in vitro cell uptake experiments. The tumor models containing RIN-M5F, INS-1, and AR42J demonstrated uptake of [\u003csup\u003e68\u003c/sup\u003eGa]Ga-DOTA-exendin-4-TOC at 60 and 120 minutes, according to microPET/CT imaging. Higher values of tumor uptake were noted for AR42J at 1.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 (120 min), INS-1 at 1.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 (60 min), and RIN-M5F at 0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 (60 min). All three tumor models exhibited tumor tissues' uptake of [\u003csup\u003e68\u003c/sup\u003eGa]Ga-DOTA-exendin-4-TOC, according to in vivo metabolism studies. Furthermore, the kidneys had the highest distribution of radioactivity.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this work, a new molecular probe that targets SSTR and GLP-1R was successfully constructed and radiolabeled with [\u003csup\u003e68\u003c/sup\u003eGa]Ga, called [\u003csup\u003e68\u003c/sup\u003eGa]Ga-DOTA-exendin-4-TOC. This novel dual-target probe could be applied as a valuable tool for improving the detection rate in patients in the future.\u003c/p\u003e","manuscriptTitle":"Synthesis and Preclinical Evaluation of Novel 68Ga-Labeled Bispecific SSTR/GLP-1R Targeting Probes for Neuroendocrine Neoplasms Imaging","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-31 15:00:43","doi":"10.21203/rs.3.rs-4317886/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"26de1f8b-41b9-4a30-8593-e761f2921f14","owner":[],"postedDate":"May 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-17T16:23:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-31 15:00:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4317886","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4317886","identity":"rs-4317886","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}