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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Bibliographic Details
Published in:Medicinal chemistry research 2023, Vol.32 (6), p.1178-1189
Main Authors: Ebrahimi, Fatemeh, Noaparast, Zohreh, Hosseinimehr, Seyed Jalal
Format: Article
Language:English
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
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Summary: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
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-023-03067-1