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dc.contributor.authorOrcutt, Kelly D-
dc.contributor.authorAdams, Gregory P-
dc.contributor.authorWu, Anna M-
dc.contributor.authorSilva, Matthew D-
dc.contributor.authorHarwell, Catey-
dc.contributor.authorHoppin, Jack-
dc.contributor.authorMatsumura, Manabu-
dc.contributor.authorKotsuma, Masakatsu-
dc.contributor.authorGreenberg, Jonathan-
dc.contributor.authorScott, Andrew M-
dc.contributor.authorBeckman, Robert A-
dc.identifier.citationMolecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging 2017; 19(5): 656-664-
dc.description.abstractCompetitive radiolabeled antibody imaging can determine the unlabeled intact antibody dose that fully blocks target binding but may be confounded by heterogeneous tumor penetration. We evaluated the hypothesis that smaller radiolabeled constructs can be used to more accurately evaluate tumor expressed receptors. The Krogh cylinder distributed model, including bivalent binding and variable intervessel distances, simulated distribution of smaller constructs in the presence of increasing doses of labeled antibody forms. Smaller constructs <25 kDa accessed binding sites more uniformly at large distances from blood vessels compared with larger constructs and intact antibody. These observations were consistent for different affinity and internalization characteristics of constructs. As predicted, a higher dose of unlabeled intact antibody was required to block binding to these distant receptor sites. Small radiolabeled constructs provide more accurate information on total receptor expression in tumors and reveal the need for higher antibody doses for target receptor blockade.-
dc.subjectAntibody imaging-
dc.subjectAntibody scaffolds-
dc.subjectMathematical model-
dc.subjectReceptor occupancy-
dc.subjectTumor antigen-
dc.subjectTumor penetration-
dc.titleMolecular Simulation of Receptor Occupancy and Tumor Penetration of an Antibody and Smaller Scaffolds: Application to Molecular Imaging.-
dc.typeJournal Article-
dc.typeResearch Support, Non-U.S. Gov't-
dc.identifier.journaltitleMolecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging-
dc.identifier.affiliationinviCRO, LLC Boston, Boston, MA, USA-
dc.identifier.affiliationDevelopmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA-
dc.identifier.affiliationViventia Bio, Philadelphia, PA, USA-
dc.identifier.affiliationDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA-
dc.identifier.affiliationRD Division of Daiichi Sankyo Co., Ltd., Tokyo, Japan-
dc.identifier.affiliationDaiichi Sankyo Pharmaceutical Development, Edison, NJ, USA-
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia-
dc.identifier.affiliationDepartment of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australia-
dc.identifier.affiliationLa Trobe University, Melbourne, Australia-
dc.identifier.affiliationDepartment of Oncology, Georgetown University Medical Center, Washington, DC, USA-
dc.identifier.affiliationDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USA-
dc.identifier.affiliationLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA-
dc.identifier.affiliationInnovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA-
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