Evaluation of homodimer 99mTc-HYNIC-E(SSSLTVPWY)2 peptide on HER2-over expressed breast cancer cells
The evidence resulting from a previous preclinical study of dimer LTVPWY peptide (99mTc-DLY) has proved the capability of the tracer to recognize overexpressed-HER2 on ovarian SKOV-3 tumor more specifically than its monomer counterpart (99mTc-LY). In present work, we compared HER2-directed DLY and LY peptides conjugated to 99mTc-HYNIC on SKBR-3 breast cancer cell to confirm HER2-targeting of 99mTc-DLY in breast cancerous tumors. New dimer construction of 99mTc-HYNIC-E(SSSLTVPWY)2 was labeled with a mixture of EDDA/tricine exchanging co-ligands. Afterward, it was utilized for evaluation of binding and specific binding uptakes besides, assessing the in vitro binding affinity ($ K_{d} $) on SKBR-3 with high density of overexpressed-HER2. 99mTc-DLY and 99mTc-LY with high RCP (>98%), displayed excellent HER2-binding specificity. The competitive binding assay revealed a reliable affinity of 2.7 nM for the 99mTc-LY monomer and 2.2 nM for the 99mTc-DLY dimer. $ B_{max} $ was calculated at (3.3 ± 0.2) × $ 10^{4} $ sites/cell and (2.6 ± 0.1) × $ 10^{5} $ sites/cell, respectively. 99mTc-LY and 99mTc-DLY exhibited about 30- and 50-fold higher uptake on SKBR-3, respectively compared to negative control cell line. The blocking experiment showed, respectively, 64% and 58% inhibition of dimer and monomer uptake using Herceptin mAbs as HER2-specific targeting agent. The findings of present investigation proved that the 99mTc-DLY specifically recognizes overexpressed-HER2 in breast cancer cells. Graphical Abstract.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
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| Enthalten in: |
Medicinal chemistry research - 32(2023), 6 vom: 06. Mai, Seite 1178-1189 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ebrahimi, Fatemeh [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Breast cancer |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s00044-023-03067-1 |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The evidence resulting from a previous preclinical study of dimer LTVPWY peptide (99mTc-DLY) has proved the capability of the tracer to recognize overexpressed-HER2 on ovarian SKOV-3 tumor more specifically than its monomer counterpart (99mTc-LY). In present work, we compared HER2-directed DLY and LY peptides conjugated to 99mTc-HYNIC on SKBR-3 breast cancer cell to confirm HER2-targeting of 99mTc-DLY in breast cancerous tumors. New dimer construction of 99mTc-HYNIC-E(SSSLTVPWY)2 was labeled with a mixture of EDDA/tricine exchanging co-ligands. Afterward, it was utilized for evaluation of binding and specific binding uptakes besides, assessing the in vitro binding affinity ($ K_{d} $) on SKBR-3 with high density of overexpressed-HER2. 99mTc-DLY and 99mTc-LY with high RCP (>98%), displayed excellent HER2-binding specificity. The competitive binding assay revealed a reliable affinity of 2.7 nM for the 99mTc-LY monomer and 2.2 nM for the 99mTc-DLY dimer. $ B_{max} $ was calculated at (3.3 ± 0.2) × $ 10^{4} $ sites/cell and (2.6 ± 0.1) × $ 10^{5} $ sites/cell, respectively. 99mTc-LY and 99mTc-DLY exhibited about 30- and 50-fold higher uptake on SKBR-3, respectively compared to negative control cell line. The blocking experiment showed, respectively, 64% and 58% inhibition of dimer and monomer uptake using Herceptin mAbs as HER2-specific targeting agent. The findings of present investigation proved that the 99mTc-DLY specifically recognizes overexpressed-HER2 in breast cancer cells. Graphical Abstract | ||
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