Preparation and biological evaluation of 99mTc-HYNIC-H1299.2 peptide for targeting and imaging of ovarian cancer

Background: Targeted molecular imaging techniques have become indispensable tools in modern diagnostics because they provide accurate and specific diagnosis of disease information. Peptides are known a class of targeting agents that could be used as molecular imaging tools.Methods: In this study, the modified peptide Ac-H1299.2 (YAAWPASGAWTGTAP) was selected and conjugated with HYNIC via lysine amino acid on C-terminus and labeled with 99mTc using tricine and EDDA as the co-ligands. These radiotracers were evaluated for potential use in diagnostic imaging of ovarian cancer cells (SKOV-3). The cell-specificity of these radiolabeled peptides was determined by their binding on an ovarian cancer cell line (SKOV-3) also displayed low affinity for lung adenocarcinoma cell line (A549) and breast cancer cell line (MCF7). Biodistributions were showed in normal and nude mice bearing SKOV-3 ovarian cell line. Finally, we demonstrated the tumor targeting in (SKOV-3) xenografted nude mice by SPECT imaging.Results: Both 99mTc-labeled peptides were labeled with 99mTc with more than 98% efficiency and were showed high stability in buffer and serum. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 3.27 ± 0.48% and 1.55 ± 0.24% for tricine and 2.34 ± 1.11% and 1.09 ± 0.18% for EDDA/ tricine at 1 and 4 h after injection, respectively. However, tumor uptakes were similar for both peptides at 1 h postinjection, a higher tumor to background ratio and lower radioactivity in the blood were observed for EDDA/ tricine co-ligands, leading to clear tumor visualization in imaging with injection of this peptide.Conclusion: This new radiopeptide was selectively targeted for ovarian cancer, and introduction of a (EDDA/ tricine) as co-ligand improved the pharmacokinetics of 99mTc labeled H1299.2 for tumor imaging in animals.

Keywords:

Tumor imaging , 99mTc , peptide , ovarian cancer