Evaluation of homodimer 99mTc-HYNIC-E(SSSLTVPWY)2 peptide on HER2-over expressed breast cancer cells

AbstractThe 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 to99mTc-HYNIC on SKBR-3 breast cancer cell to confirm HER2-targeting of99mTc-DLY in breast cancerous tumors. New dimer construction of99mTc-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 (Kd) on SKBR-3 with high density of overexpressed-HER2.99mTc-DLY and99mTc-LY with high RCP (>98%), displayed excellent HER2-binding specificity. The competitive binding assay revealed a reliable affinity of 2.7  nM for the99mTc-LY monomer and 2.2  nM for the99mTc-DLY dimer. Bmax was calculated at (3.3  ± 0.2) × 104 sites/cell and (2.6  ± 0.1) × 105 sites/cell, respectively.99mTc-LY and99mTc-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 the99mTc-DLY specifically recognizes overexpressed-HER2 in breast cancer cells.Graph...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research