Effect of using different co-ligands during ۹۹mTc-labeling of J۱۸ peptide on SK-MES-۱ cell binding and tumor targeting

Objective(s): Lung cancer is the main cause of cancer death, and its incidence is increasing worldwide. The goal of this study is to evaluate in vitro and in vivo tumor targeting behavior of [۹۹mTc]Tc -HYNIC-(Ser)۳-J۱۸ in lung carcinoma (SK-MES-۱)-bearing mice.Materials and Methods: The J۱۸ (RSLWSDFYASASRGP) peptide was conjugated with hydrazinonicotinamide (HYNIC) via three serine amino acids as a linker at the peptide’s N-terminal and then labeled with technetium-۹۹m using tricine and tricine/EDDA as the co-ligands. The radiolabeled peptides were assessed for in vitro receptor binding, specific binding, and saturation affinity. In vivo biodistribution studies were also performed for ۹۹mTc-peptide ۱ (tricine co-ligand) and ۹۹mTc-peptide ۲ (tricine/EDDA coligands) in nude mice bearing SK-MES-۱ xenograft tumors. Results: In vitro studies showed high specific binding for ۹۹mTc-peptide ۱ in SKMES-۱ cells compared with ۹۹mTc-peptide ۲ (۱۱.۵ vs. ۴.۵). The Kd values for ۹۹mTc-peptide ۱ and ۹۹mTc-peptide ۲ were reported to be ۳.۱±۰.۳ nM and ۳.۴۶ ± ۰.۸ nM, respectively.  The biodistribution study also showed high significant tumor to muscle ratios were ۵.۱ and ۶.۱۸ for ۹۹mTc-peptide ۱ at ۱ and ۲ hr after injection, respectively, while these ratios were ۳.۸۱ and ۵.۱۸ for peptide ۲, respectively. Conclusion: Overall, ۹۹mTc-labeled J۱۸ peptide in the presence of tricine as co-ligand has better in vitro and in vivo tumor targeting properties in SK-MES-۱ cells than tricine/EDDA co-ligands. These findings show that the ۹۹mTc-labeled J۱۸ peptide is a good candidate for lung carcinoma targeting.

Keywords:

[۹۹mTc ]Tc-HYNIC-(Ser)۳-J۱۸ , EDDA , HYNIC-SSS-J۱۸ , Linker , Lung carcinoma targeting , NSCLC , Tricine