Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9517
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dc.contributor.authorMitchell, Paul L Ren
dc.contributor.authorLee, Fook-Theanen
dc.contributor.authorHall, Cathrineen
dc.contributor.authorRigopoulos, Angelaen
dc.contributor.authorSmyth, Fiona Een
dc.contributor.authorHekman, Anne-Marieen
dc.contributor.authorvan Schijndel, Gijs Men
dc.contributor.authorPowles, Rayen
dc.contributor.authorBrechbiel, Martin Wen
dc.contributor.authorScott, Andrew Men
dc.date.accessioned2015-05-15T22:38:23Z
dc.date.available2015-05-15T22:38:23Z
dc.date.issued2003-07-01en
dc.identifier.citationJournal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine; 44(7): 1105-12en
dc.identifier.govdoc12843229en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/9517en
dc.description.abstractThe Philadelphia chromosome translocation (Ph(+)) confers a poor prognosis in patients with acute lymphocytic leukemia (ALL). CD19 is highly expressed (CD19(+)) on ALL cells and is an attractive target for antibody-based therapies. CLB-CD19 is an IgG1kappa murine monoclonal antibody (mAb) directed against an epitope on the CD19 antigen.Radiolabeled CLB-CD19 antibody was evaluated for targeting ALL in a severe combined immunodeficient (SCID) mouse model engrafted with primary human leukemia cells. Lodgment of CD19(+) ALL cells in spleen and liver was confirmed using immunohistochemistry analyses. Circulating CD19(+) ALL cells in blood were also detected by flow cytometry.Antibody was labeled directly with the radiohalogen (125)I and radiometal (111)In via the bifunctional metal ion chelate CHX-A"-diethylenetriaminepentaacetic acid (DTPA) with retention of immunoreactivities. After intravenous injection of radioconjugates, biodistribution studies showed rapid localization of the (111)In-conjugate to leukemia-infiltrated spleen, reaching a maximum (mean +/- SD) of 72.78 +/- 13.67 % injected dose per gram of tissue (%ID/g) by 24 h after injection. In contrast, peak localization of coinjected (125)I-CLB-CD19 occurred by 4 h and was significantly lower (11.41 +/- 12.79 %ID/g) (P < 0.001). Uptake of (111)In-conjugate in the liver containing tumor was also evident but not in other normal tissues. Uptake of radiolabeled CLB-CD19 in tumor-bearing organs was specific, as uptake of radiolabeled isotype-matched antibody control was low. Gamma-camera imaging detected the uptake of (111)In-CHX-A"-DTPA CLB-CD19 in enlarged tumor-bearing spleen of engrafted mice. A single injection of 32 micro g CLB-CD19 mAb had a delayed suppressive effect on the level of circulatory leukemia cells in surviving mice and extended the median survival from 48.5 to 58 d (n = 8; P = 0.03).The radiolabeled anti-CD19 antibody showed specific targeting and rapid internalization in ALL cell-engrafted SCID mice and may also be used for selective intracellular delivery of cytotoxic radionuclides with beta-, Auger, or alpha-emissions.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherAntibodies, Monoclonal.chemistry.pharmacokineticsen
dc.subject.otherAntigens, CD19.metabolismen
dc.subject.otherHumansen
dc.subject.otherIndium Radioisotopes.pharmacokineticsen
dc.subject.otherIodine Radioisotopes.pharmacokineticsen
dc.subject.otherIsotope Labeling.methodsen
dc.subject.otherLeukemia, Myelogenous, Chronic, BCR-ABL Positive.metabolism.pathology.radionuclide imagingen
dc.subject.otherMiceen
dc.subject.otherMice, SCIDen
dc.subject.otherNeoplasm Transplantationen
dc.subject.otherPrecursor Cell Lymphoblastic Leukemia-Lymphoma.metabolism.pathology.radionuclide imagingen
dc.subject.otherRecombinant Proteins.chemistry.pharmacokineticsen
dc.subject.otherSpleen.metabolismen
dc.subject.otherSplenic Neoplasms.metabolismen
dc.subject.otherTissue Distributionen
dc.subject.otherTumor Markers, Biological.metabolismen
dc.titleTargeting primary human Ph(+) B-cell precursor leukemia-engrafted SCID mice using radiolabeled anti-CD19 monoclonal antibodies.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of Nuclear Medicineen
dc.identifier.affiliationLudwig Institute For Cancer Research, Melbourne Tumour Biology Branch, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australiaen
dc.description.pages1105-12en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/12843229en
dc.type.austinJournal Articleen
local.name.researcherMitchell, Paul L R
item.languageiso639-1en-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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