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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 ( 99m Tc-DLY) has proved the capability of the tracer to recognize overexpressed-HER2 on ovarian SKOV-3 tumor more specifically than its monomer counterpart ( 99m Tc-LY). In present work, we compared HER2-directed DLY a...
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Published in: | Medicinal chemistry research 2023-06, Vol.32 (6), p.1178-1189 |
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description | The evidence resulting from a previous preclinical study of dimer LTVPWY peptide (
99m
Tc-DLY) has proved the capability of the tracer to recognize overexpressed-HER2 on ovarian SKOV-3 tumor more specifically than its monomer counterpart (
99m
Tc-LY). In present work, we compared HER2-directed DLY and LY peptides conjugated to
99m
Tc-HYNIC on SKBR-3 breast cancer cell to confirm HER2-targeting of
99m
Tc-DLY in breast cancerous tumors. New dimer construction of
99m
Tc-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.
99m
Tc-DLY and
99m
Tc-LY with high RCP (>98%), displayed excellent HER2-binding specificity. The competitive binding assay revealed a reliable affinity of 2.7 nM for the
99m
Tc-LY monomer and 2.2 nM for the
99m
Tc-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.
99m
Tc-LY and
99m
Tc-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
99m
Tc-DLY specifically recognizes overexpressed-HER2 in breast cancer cells.
Graphical Abstract |
doi_str_mv | 10.1007/s00044-023-03067-1 |
format | article |
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99m
Tc-DLY) has proved the capability of the tracer to recognize overexpressed-HER2 on ovarian SKOV-3 tumor more specifically than its monomer counterpart (
99m
Tc-LY). In present work, we compared HER2-directed DLY and LY peptides conjugated to
99m
Tc-HYNIC on SKBR-3 breast cancer cell to confirm HER2-targeting of
99m
Tc-DLY in breast cancerous tumors. New dimer construction of
99m
Tc-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.
99m
Tc-DLY and
99m
Tc-LY with high RCP (>98%), displayed excellent HER2-binding specificity. The competitive binding assay revealed a reliable affinity of 2.7 nM for the
99m
Tc-LY monomer and 2.2 nM for the
99m
Tc-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.
99m
Tc-LY and
99m
Tc-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
99m
Tc-DLY specifically recognizes overexpressed-HER2 in breast cancer cells.
Graphical Abstract</description><identifier>ISSN: 1054-2523</identifier><identifier>EISSN: 1554-8120</identifier><identifier>DOI: 10.1007/s00044-023-03067-1</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Affinity ; Binding ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Bioorganic Chemistry ; Breast cancer ; Dimers ; ErbB-2 protein ; Inorganic Chemistry ; Medicinal Chemistry ; Monomers ; Original Research ; Peptides ; Pharmacology/Toxicology ; Tumors</subject><ispartof>Medicinal chemistry research, 2023-06, Vol.32 (6), p.1178-1189</ispartof><rights>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.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c200t-e7a2bd0aa72dd69015523c9410e1437d6f1eed91b2b61ab8ec45455212f0a0d83</cites><orcidid>0000-0001-8055-8036</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids></links><search><creatorcontrib>Ebrahimi, Fatemeh</creatorcontrib><creatorcontrib>Noaparast, Zohreh</creatorcontrib><creatorcontrib>Hosseinimehr, Seyed Jalal</creatorcontrib><title>Evaluation of homodimer 99mTc-HYNIC-E(SSSLTVPWY)2 peptide on HER2-over expressed breast cancer cells</title><title>Medicinal chemistry research</title><addtitle>Med Chem Res</addtitle><description>The evidence resulting from a previous preclinical study of dimer LTVPWY peptide (
99m
Tc-DLY) has proved the capability of the tracer to recognize overexpressed-HER2 on ovarian SKOV-3 tumor more specifically than its monomer counterpart (
99m
Tc-LY). In present work, we compared HER2-directed DLY and LY peptides conjugated to
99m
Tc-HYNIC on SKBR-3 breast cancer cell to confirm HER2-targeting of
99m
Tc-DLY in breast cancerous tumors. New dimer construction of
99m
Tc-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.
99m
Tc-DLY and
99m
Tc-LY with high RCP (>98%), displayed excellent HER2-binding specificity. The competitive binding assay revealed a reliable affinity of 2.7 nM for the
99m
Tc-LY monomer and 2.2 nM for the
99m
Tc-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.
99m
Tc-LY and
99m
Tc-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
99m
Tc-DLY specifically recognizes overexpressed-HER2 in breast cancer cells.
Graphical Abstract</description><subject>Affinity</subject><subject>Binding</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bioorganic Chemistry</subject><subject>Breast cancer</subject><subject>Dimers</subject><subject>ErbB-2 protein</subject><subject>Inorganic Chemistry</subject><subject>Medicinal Chemistry</subject><subject>Monomers</subject><subject>Original Research</subject><subject>Peptides</subject><subject>Pharmacology/Toxicology</subject><subject>Tumors</subject><issn>1054-2523</issn><issn>1554-8120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kEtLA0EQhAdRMEb_gKcFL3oY7Xns6yghmkBQMVHJaZjd6dWVfTmzCfrvnbiCN09dNF9VN0XIKYNLBhBfOQCQkgIXFAREMWV7ZMTCUNKEcdj3GrzmIReH5Mi5dwARgwxHxEy3utrovmyboC2Ct7ZuTVmjDdK0XuV0tr6bT-j0fLlcLlbPDy_rCx502PWlwcA7ZtNHTtutx_Gzs-gcmiCzqF0f5LrJ_T7HqnLH5KDQlcOT3zkmTzfT1WRGF_e388n1guYcoKcYa54Z0DrmxkQp-P-5yFPJAJkUsYkKhmhSlvEsYjpLMJeh9AzjBWgwiRiTsyG3s-3HBl2v3tuNbfxJxRMuhYgTyTzFByq3rXMWC9XZstb2SzFQuzbV0KbybaqfNtXOJAaT83DzivYv-h_XN2OwdUM</recordid><startdate>20230601</startdate><enddate>20230601</enddate><creator>Ebrahimi, Fatemeh</creator><creator>Noaparast, Zohreh</creator><creator>Hosseinimehr, Seyed Jalal</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0001-8055-8036</orcidid></search><sort><creationdate>20230601</creationdate><title>Evaluation of homodimer 99mTc-HYNIC-E(SSSLTVPWY)2 peptide on HER2-over expressed breast cancer cells</title><author>Ebrahimi, Fatemeh ; Noaparast, Zohreh ; Hosseinimehr, Seyed Jalal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c200t-e7a2bd0aa72dd69015523c9410e1437d6f1eed91b2b61ab8ec45455212f0a0d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Affinity</topic><topic>Binding</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bioorganic Chemistry</topic><topic>Breast cancer</topic><topic>Dimers</topic><topic>ErbB-2 protein</topic><topic>Inorganic Chemistry</topic><topic>Medicinal Chemistry</topic><topic>Monomers</topic><topic>Original Research</topic><topic>Peptides</topic><topic>Pharmacology/Toxicology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ebrahimi, Fatemeh</creatorcontrib><creatorcontrib>Noaparast, Zohreh</creatorcontrib><creatorcontrib>Hosseinimehr, Seyed Jalal</creatorcontrib><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Medicinal chemistry research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ebrahimi, Fatemeh</au><au>Noaparast, Zohreh</au><au>Hosseinimehr, Seyed Jalal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of homodimer 99mTc-HYNIC-E(SSSLTVPWY)2 peptide on HER2-over expressed breast cancer cells</atitle><jtitle>Medicinal chemistry research</jtitle><stitle>Med Chem Res</stitle><date>2023-06-01</date><risdate>2023</risdate><volume>32</volume><issue>6</issue><spage>1178</spage><epage>1189</epage><pages>1178-1189</pages><issn>1054-2523</issn><eissn>1554-8120</eissn><abstract>The evidence resulting from a previous preclinical study of dimer LTVPWY peptide (
99m
Tc-DLY) has proved the capability of the tracer to recognize overexpressed-HER2 on ovarian SKOV-3 tumor more specifically than its monomer counterpart (
99m
Tc-LY). In present work, we compared HER2-directed DLY and LY peptides conjugated to
99m
Tc-HYNIC on SKBR-3 breast cancer cell to confirm HER2-targeting of
99m
Tc-DLY in breast cancerous tumors. New dimer construction of
99m
Tc-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.
99m
Tc-DLY and
99m
Tc-LY with high RCP (>98%), displayed excellent HER2-binding specificity. The competitive binding assay revealed a reliable affinity of 2.7 nM for the
99m
Tc-LY monomer and 2.2 nM for the
99m
Tc-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.
99m
Tc-LY and
99m
Tc-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
99m
Tc-DLY specifically recognizes overexpressed-HER2 in breast cancer cells.
Graphical Abstract</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s00044-023-03067-1</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8055-8036</orcidid></addata></record> |
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subjects | Affinity Binding Biochemistry Biomedical and Life Sciences Biomedicine Bioorganic Chemistry Breast cancer Dimers ErbB-2 protein Inorganic Chemistry Medicinal Chemistry Monomers Original Research Peptides Pharmacology/Toxicology Tumors |
title | Evaluation of homodimer 99mTc-HYNIC-E(SSSLTVPWY)2 peptide on HER2-over expressed breast cancer cells |
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