Effect of using different co-ligands during 99mTc-labeling of J18 peptide on SK-MES-1 cell binding and tumor targeting

Document Type : Original Article

Authors

1 Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

2 Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

3 Department of Nuclear Medicine and Molecular Imaging, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

4 Department of Nuclear Medicine and Molecular Imaging, Clinical Development Research Unit of Farshchian Heart Center, Hamadan University of Medical Sciences, Hamadan, Iran

Abstract

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 [99mTc]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 99mTc-peptide 1 (tricine co-ligand) and 99mTc-peptide 2 (tricine/EDDA coligands) in nude mice bearing SK-MES-1 xenograft tumors.
Results: In vitro studies showed high specific binding for 99mTc-peptide 1 in SKMES-1 cells compared with 99mTc-peptide 2 (11.5 vs. 4.5). The Kd values for 99mTc-peptide 1 and 99mTc-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 were 5.1 and 6.18 for 99mTc-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, 99mTc-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 99mTc-labeled J18 peptide is a good candidate for lung carcinoma targeting.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 24, Issue 9
September 2021
Pages 1240-1246

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