Amplified delivery of indium-111 to EGFR-positive human breast cancer cells.

A method is described to amplify the delivery of 111In to human breast cancer cells utilizing a novel human serum albumin-human EGF (HSA-hEGF) bioconjugate substituted preferentially in the HSA domain with multiple DTPA metal chelators for 111In. 111In-DTPA-HSA-hEGF exhibited a lower receptor-bindin...

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Päätekijät: Wang, J, Chen, P, Su, Z, Vallis, K, Sandhu, J, Cameron, R, Hendler, A, Reilly, R
Aineistotyyppi: Journal article
Kieli:English
Julkaistu: 2001
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author Wang, J
Chen, P
Su, Z
Vallis, K
Sandhu, J
Cameron, R
Hendler, A
Reilly, R
author_facet Wang, J
Chen, P
Su, Z
Vallis, K
Sandhu, J
Cameron, R
Hendler, A
Reilly, R
author_sort Wang, J
collection OXFORD
description A method is described to amplify the delivery of 111In to human breast cancer cells utilizing a novel human serum albumin-human EGF (HSA-hEGF) bioconjugate substituted preferentially in the HSA domain with multiple DTPA metal chelators for 111In. 111In-DTPA-HSA-hEGF exhibited a lower receptor-binding affinity than 111In-DTPA-hEGF but was rapidly and specifically bound, internalized and translocated to the nucleus in EGFR-positive MDA-MB-468 breast cancer cells. 111In-DTPA-HSA-hEGF was cytotoxic in vitro mainly through the emission of short-range Auger electrons and partially through the effects of the hEGF moiety to MDA-MB-468 cells overexpressing EGFR (1-2 x 10(6) receptors/cell) but not towards MCF-7 breast cancer cells with a 100-fold lower level of EGFR on their surface. The cytotoxicity in vitro against MDA-MB-468 cells of 111In-DTPA-HSA-hEGF substituted with nine DTPA chelators was enhanced 4-fold compared to 111In-DTPA-hEGF monosubstituted with DTPA. Studies are planned to further evaluate 111In-DTPA-HSA-hEGF in vivo as a new imaging and targeted radiotherapeutic agent for breast cancer.
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spelling oxford-uuid:a2eb0f1b-52fb-480d-ab83-0d5fcb231b642022-03-27T02:23:15ZAmplified delivery of indium-111 to EGFR-positive human breast cancer cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a2eb0f1b-52fb-480d-ab83-0d5fcb231b64EnglishSymplectic Elements at Oxford2001Wang, JChen, PSu, ZVallis, KSandhu, JCameron, RHendler, AReilly, RA method is described to amplify the delivery of 111In to human breast cancer cells utilizing a novel human serum albumin-human EGF (HSA-hEGF) bioconjugate substituted preferentially in the HSA domain with multiple DTPA metal chelators for 111In. 111In-DTPA-HSA-hEGF exhibited a lower receptor-binding affinity than 111In-DTPA-hEGF but was rapidly and specifically bound, internalized and translocated to the nucleus in EGFR-positive MDA-MB-468 breast cancer cells. 111In-DTPA-HSA-hEGF was cytotoxic in vitro mainly through the emission of short-range Auger electrons and partially through the effects of the hEGF moiety to MDA-MB-468 cells overexpressing EGFR (1-2 x 10(6) receptors/cell) but not towards MCF-7 breast cancer cells with a 100-fold lower level of EGFR on their surface. The cytotoxicity in vitro against MDA-MB-468 cells of 111In-DTPA-HSA-hEGF substituted with nine DTPA chelators was enhanced 4-fold compared to 111In-DTPA-hEGF monosubstituted with DTPA. Studies are planned to further evaluate 111In-DTPA-HSA-hEGF in vivo as a new imaging and targeted radiotherapeutic agent for breast cancer.
spellingShingle Wang, J
Chen, P
Su, Z
Vallis, K
Sandhu, J
Cameron, R
Hendler, A
Reilly, R
Amplified delivery of indium-111 to EGFR-positive human breast cancer cells.
title Amplified delivery of indium-111 to EGFR-positive human breast cancer cells.
title_full Amplified delivery of indium-111 to EGFR-positive human breast cancer cells.
title_fullStr Amplified delivery of indium-111 to EGFR-positive human breast cancer cells.
title_full_unstemmed Amplified delivery of indium-111 to EGFR-positive human breast cancer cells.
title_short Amplified delivery of indium-111 to EGFR-positive human breast cancer cells.
title_sort amplified delivery of indium 111 to egfr positive human breast cancer cells
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