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dc.contributor.authorKelly, Marcus Pen
dc.contributor.authorLee, Fook-Theanen
dc.contributor.authorTahtis, Kikien
dc.contributor.authorPower, David Anthonyen
dc.contributor.authorSmyth, Fiona Een
dc.contributor.authorBrechbiel, Martin Wen
dc.contributor.authorHudson, Peter Jen
dc.contributor.authorScott, Andrew Men
dc.identifier.citationCancer Biotherapy & Radiopharmaceuticals; 23(4): 411-23en
dc.description.abstractThe use of single-chain variable fragment (scFv) constructs has been investigated in cancer radioimmunotherapy (RIT) and radioimmunodetection, as these molecules permit rapid tumor penetration and clearance from the serum relative to whole IgG. Multimerization of scFv constructs has demonstrated improvements in functional affinity (i.e., avidity) and maximal tumor uptake. In this paper, we report the first biodistribution and pharmacokinetics studies of a noncovalent, direct-linked scFv (V(L)-0-V(H)) trimeric/tetrameric "multimer" of the anti-Lewis Y monoclonal antibody, hu3S193. The in vitro binding and in vivo biodistribution of the hu3S193 multimer was characterized alongside the hu3S193 F(ab')(2) following radiolabeling with the Indium-111 ((111)In) radioisotope. Immunoreactivities of the radiolabeled multimer and F(ab')(2) were 73% and 53.2%, and binding affinities (K(a)) were 1.58 x 10(7) M(1) and 4.31 x 10(6) M (1) for the multimer and F(ab')(2), respectively. Maximal tumor uptake in Le(y)-positive MCF-7 breast cancer xenografted BALB/c nude mice was 12.6 +/- 2.5 percent injected dose/per gram (%ID/g) at 6 hours postinjection for the multimer and 15.7 +/- 2.1 %ID/g at 24 hours postinjection for the F(ab')(2). However, limited in vitro stability and high renal localization of radiolabeled constructs were observed, which, despite the observed tumor targeting of the hu3S193 multimer, most likely preclude its use in RIT and imaging modalities.en
dc.subject.otherAntibodies, Monoclonal.chemistry.geneticsen
dc.subject.otherAntibodies, Monoclonal, Humanizeden
dc.subject.otherArea Under Curveen
dc.subject.otherCell Line, Tumoren
dc.subject.otherChromatography, Gelen
dc.subject.otherDrug Stabilityen
dc.subject.otherImmunoglobulin Fab Fragments.chemistry.immunology.metabolismen
dc.subject.otherImmunoglobulin Variable Region.genetics.immunology.metabolismen
dc.subject.otherIndium Radioisotopesen
dc.subject.otherLewis Blood-Group System.immunologyen
dc.subject.otherMammary Neoplasms, Experimental.immunology.metabolism.radionuclide imagingen
dc.subject.otherMice, Inbred BALB Cen
dc.subject.otherMice, Nudeen
dc.subject.otherNeoplasms.immunology.metabolism.radionuclide imagingen
dc.subject.otherRadionuclide Imagingen
dc.subject.otherRecombinant Proteins.blood.immunology.pharmacokineticsen
dc.subject.otherTissue Distributionen
dc.subject.otherTransplantation, Heterologousen
dc.titleTumor targeting by a multivalent single-chain Fv (scFv) anti-Lewis Y antibody construct.en
dc.typeJournal Articleen
dc.identifier.journaltitleCancer biotherapy & radiopharmaceuticalsen
dc.identifier.affiliationTumour Targeting Program, Ludwig Institute for Cancer Research, Austin Hospital, Heidelberg, Victoria, Australiaen
dc.type.austinJournal Articleen, Andrew M
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.languageiso639-1en- Imaging and Therapy- Newton-John Cancer Research Institute-
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