Effect of using different co-ligands during (99m)Tc-labeling of J18 peptide on SK-MES-1 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 [(99m)Tc]Tc -HYNIC-(Ser)(3)-J18 in lung carcinoma (SK-MES-1)-bearing mice. MATERIALS AND METHODS: The J18 (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-99m 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 (99m)Tc-peptide 1 (tricine co-ligand) and (99m)Tc-peptide 2 (tricine/EDDA coligands) in nude mice bearing SK-MES-1 xenograft tumors. RESULTS: In vitro studies showed high specific binding for (99m)Tc-peptide 1 in SKMES-1 cells compared with (99m)Tc-peptide 2 (11.5 vs. 4.5). The K(D) values for (99m)Tc-peptide 1 and (99m)Tc-peptide 2 were reported to be 3.1±0.3 nM and 3.46 ± 0.8 nM, respectively. The biodistribution study also showed high significant tumor to muscle ratios of 5.1 and 6.18 for (99m)Tc-peptide 1 at 1 and 2 hr after injection, respectively, while these ratios were 3.81 and 5.18 for peptide 2, respectively. CONCLUSION: Overall, (99m)Tc-labeled J18 peptide in the presence of tricine as co-ligand has better in vitro and in vivo tumor targeting properties in SK-MES-1 cells than tricine/EDDA co-ligands. These findings show that the (99m)Tc-labeled J18 peptide is a good candidate for lung carcinoma targeting.