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dc.contributor.authorLobeek, Den_US
dc.contributor.authorFranssen, GMen_US
dc.contributor.authorMa, MTen_US
dc.contributor.authorWester, H-Jen_US
dc.contributor.authorDecristoforo, Cen_US
dc.contributor.authorOyen, WJGen_US
dc.contributor.authorBoerman, OCen_US
dc.contributor.authorTerry, SYAen_US
dc.contributor.authorRijpkema, Men_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2018-11-14T09:15:04Z
dc.date.issued2018-08en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29626124en_US
dc.identifierjnumed.117.206979en_US
dc.identifier.citationJ Nucl Med, 2018, 59 (8), pp. 1296 - 1301en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2925
dc.identifier.eissn1535-5667en_US
dc.identifier.doi10.2967/jnumed.117.206979en_US
dc.description.abstractαvβ3 integrins play an important role in angiogenesis and cell migration in cancer and are highly expressed on the activated endothelial cells of newly formed blood vessels. Here, we compare the targeting characteristics of 4 68Ga-labeled multimeric cyclic arginine-glycine-aspartate (RGD)-based tracers in an αvβ3 integrin-expressing tumor model and a tumor model in which αvβ3 integrin is expressed solely on the neovasculature. Methods: Female BALB/c nude mice were subcutaneously injected with SK-RC-52 (αvβ3 integrin-positive) or FaDu (αvβ3 integrin-negative) tumor cells. 68Ga-labeled DOTA-(RGD)2, TRAP-(RGD)3, FSC-(RGD)3, or THP-(RGD)3 was intravenously administered to the mice (0.5 nmol per mouse, 10-20 MBq), followed by small-animal PET/CT imaging and ex vivo biodistribution studies 1 h after injection. Nonspecific uptake of the tracers in both models was determined by coinjecting an excess of unlabeled DOTA-(RGD)2 (50 nmol) along with the radiolabeled tracers. Results: Imaging and biodistribution data showed specific uptake in the tumors for each tracer in both models. Tumor uptake of 68Ga-FSC-(RGD)3 was significantly higher than that of 68Ga-DOTA-(RGD)2, 68Ga-TRAP-(RGD)3, or 68Ga-THP-(RGD)3 in the SK-RC-52 model but not in the FaDu model, in which 68Ga-FSC-(RGD)3 showed significantly higher tumor uptake than 68Ga-TRAP-(RGD)3 Most importantly, differences were also observed in normal tissues and in tumor-to-blood ratios. Conclusion: All tracers showed sufficient targeting of αvβ3 integrin expression to allow for tumor detection. Although the highest tumor uptake was found for 68Ga-FSC-(RGD)3 and 68Ga-THP-(RGD)3 in the SK-RC-52 and FaDu models, respectively, selection of the optimal tracer for specific diagnostic applications also depends on tumor-to-blood ratio and uptake in normal tissues; these factors should therefore also be considered.en_US
dc.format.extent1296 - 1301en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.subject68Gaen_US
dc.subjectRGD peptidesen_US
dc.subjectangiogenesisen_US
dc.subjectmultimersen_US
dc.subjectαvβ3 integrinen_US
dc.titleIn Vivo Characterization of 4 68Ga-Labeled Multimeric RGD Peptides to Image αvβ3 Integrin Expression in 2 Human Tumor Xenograft Mouse Models.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-02-12en_US
rioxxterms.versionofrecord10.2967/jnumed.117.206979en_US
rioxxterms.licenseref.startdate2018-08en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJ Nucl Meden_US
pubs.issue8en_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/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Molecular Imaging
pubs.publication-statusPublisheden_US
pubs.volume59en_US
pubs.embargo.termsNot knownen_US
icr.researchteamTranslational Molecular Imagingen_US
dc.contributor.icrauthorOyen, Willemen_US


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