dc.contributor.author | Da Pieve, C | |
dc.contributor.author | Makarem, A | |
dc.contributor.author | Turnock, S | |
dc.contributor.author | Maczynska, J | |
dc.contributor.author | Smith, G | |
dc.contributor.author | Kramer-Marek, G | |
dc.date.accessioned | 2020-05-22T14:08:31Z | |
dc.date.issued | 2020-03-29 | |
dc.identifier.citation | Molecules (Basel, Switzerland), 2020, 25 (7) | |
dc.identifier.issn | 1420-3049 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3627 | |
dc.identifier.eissn | 1420-3049 | |
dc.identifier.doi | 10.3390/molecules25071562 | |
dc.description.abstract | Site-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. | |
dc.format | Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | MDPI | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Neuroglia | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Mice, Nude | |
dc.subject | Glioblastoma | |
dc.subject | Fluorine Radioisotopes | |
dc.subject | Acetates | |
dc.subject | Maleimides | |
dc.subject | Sulfhydryl Compounds | |
dc.subject | Heterocyclic Compounds, 1-Ring | |
dc.subject | Oxadiazoles | |
dc.subject | Immunoconjugates | |
dc.subject | Positron-Emission Tomography | |
dc.subject | Female | |
dc.subject | Heterografts | |
dc.subject | ErbB Receptors | |
dc.title | Thiol-Reactive PODS-Bearing Bifunctional Chelators for the Development of EGFR-Targeting [18F]AlF-Affibody Conjugates. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-03-27 | |
rioxxterms.versionofrecord | 10.3390/molecules25071562 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-03-29 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecules (Basel, Switzerland) | |
pubs.issue | 7 | |
pubs.notes | Not known | |
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.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.publication-status | Published | |
pubs.volume | 25 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Preclinical Molecular Imaging | |
dc.contributor.icrauthor | Da Pieve, Chiara | |
dc.contributor.icrauthor | Turnock, Stephen | |
dc.contributor.icrauthor | Smith, Graham | |
dc.contributor.icrauthor | Kramer-Marek, Gabriela | |