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dc.contributor.authorDa Pieve, Cen_US
dc.contributor.authorMakarem, Aen_US
dc.contributor.authorTurnock, Sen_US
dc.contributor.authorMaczynska, Jen_US
dc.contributor.authorSmith, Gen_US
dc.contributor.authorKramer-Marek, Gen_US
dc.date.accessioned2020-05-22T14:08:31Z
dc.date.issued2020-03-29en_US
dc.identifier.citationMolecules (Basel, Switzerland), 2020, 25 (7)en_US
dc.identifier.issn1420-3049en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3627
dc.identifier.eissn1420-3049en_US
dc.identifier.doi10.3390/molecules25071562en_US
dc.description.abstractSite-selective bioconjugation of cysteine-containing peptides and proteins is currently achieved via a maleimide-thiol reaction (Michael addition). When maleimide-functionalized chelators are used and the resulting bioconjugates are subsequently radiolabeled, instability has been observed both during radiosynthesis and post-injection in vivo, reducing radiochemical yield and negatively impacting performance. Recently, a phenyloxadiazolyl methylsulfone derivative (PODS) was proposed as an alternative to maleimide for the site-selective conjugation and radiolabeling of proteins, demonstrating improved in vitro stability and in vivo performance. Therefore, we have synthesized two novel PODS-bearing bifunctional chelators (NOTA-PODS and NODAGA-PODS) and attached them to the EGFR-targeting affibody molecule ZEGFR:03115. After radiolabeling with the aluminum fluoride complex ([18F]AlF), both conjugates showed good stability in murine serum. When injected in high EGFR-expressing tumor-bearing mice, [18F]AlF-NOTA-PODS-ZEGFR:03115 and [18F]AlF-NODAGA-PODS-ZEGFR:03115 showed similar pharmacokinetics and a specific tumor uptake of 14.1 ± 5.3% and 16.7 ± 4.5% ID/g at 1 h post-injection, respectively. The current results are encouraging for using PODS as an alternative to maleimide-based thiol-selective bioconjugation reactions.en_US
dc.formatElectronicen_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleThiol-Reactive PODS-Bearing Bifunctional Chelators for the Development of EGFR-Targeting [18F]AlF-Affibody Conjugates.en_US
dc.typeJournal Article
dcterms.dateAccepted2020-03-27en_US
rioxxterms.versionofrecord10.3390/molecules25071562en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2020-03-29en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfMolecules (Basel, Switzerland)en_US
pubs.issue7en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Preclinical Molecular Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Preclinical Molecular Imaging
pubs.publication-statusPublisheden_US
pubs.volume25en_US
pubs.embargo.termsNot knownen_US
icr.researchteamPreclinical Molecular Imagingen_US
dc.contributor.icrauthorKramer-Marek, Gabrielaen_US
dc.contributor.icrauthorTurnock, Stephenen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/