Homodimer ^99mTc-HYNIC-E(SSSLTVPWY)₂ peptide improved HER2-overexpressed tumor targeting and imaging

We hypothesized that a novel design of the LTVPWY (LY) peptide might exhibit a great potential for improving binding affinity and targeting HER2-overexpressed tumors. Hence, new dimer construction of ^99mTc-labeled LY [^99mTc-HYNIC-E(SSSLTVPWY)₂] (^99mTc-DLY) was introduced. Afterward, a head-to-head comparison of in vitro and in vivo experiments was performed between ^99mTc-DLY and ^99mTc-HYNIC-SSSLTVPWY as the monomer analog. The blocking dosage of trastuzumab reduced the uptake of the dimer about 20% more efficiently than the monomer in the SKOV-3 cell line. A twofold increase in competitive binding affinity and biological half-life was observed for ^99mTc-DLY. The ovarian-tumor-bearing mice were detected with high contrast where the tumor-to-muscle ratio of ^99mTc-DLY was notably increased about 40% using a gamma camera. The biodistribution experiment revealed an approximately 10% enhancement in tumor/blood, tumor/muscle, and tumor/bone ratios for the dimer. More rapid blood clearance was another achievement of the homodimer design. Overall, ^99mTc-DLY successfully affected the pharmacokinetics and consequently the visualization of HER2-overexpressing tumors.