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Abstract

Development of c-Met targeting probes based on specifically designed peptides with high affinity and stability could help enhance diagnostic efficacy and therapeutic effects in c-Met positive cancers. The Random non-standard Peptides Integrated Discovery (RaPID) system for synthesizing natural product-like macrocyclic peptides via in vitro translation-based selection has recently emerged to overcome the shortcomings of traditional peptide synthesis. Here, we developed non-standard macrocyclic peptides specific to c-Met, and examined the cancer-targeting efficiency of fluorescein-labeled (FL) anti-c-Met peptides, referred to as aML5-FL and aMD4-FL, both in vitro and in vivo. The aML5-FL effectively targeted SNU-638 gastric cancer cells with high c-Met expression, compared to the aMD4-FL due to its high affinity. After intravenous administration of aML5-FL in a tumor xenograft mouse model, FL signal intensity in the extracted SNU-638 tumors was higher than that in SNU-216 tumors. This study provides preclinical data for the usefulness of novel non-standard macrocyclic peptides developed by the RaPID system for specific biomarker imaging.

Author information

Hwang DW1, Bahng N2, Ito K3, Ha S1, Kim MY4, Lee E5, Suga H6, Lee DS7.

1Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Republic of Korea.

2Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Medicinal Bioconvergence Research Center, Seoul National University, Republic of Korea.

3Department of Chemistry, Graduate School of Science, The University of Tokyo, 113-0033 Tokyo, Japan.

4Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

5Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

6Department of Chemistry, Graduate School of Science, The University of Tokyo, 113-0033 Tokyo, Japan. Electronic address: hsuga@chem.s.u-tokyo.ac.jp.

7Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Republic of Korea. Electronic address: dsl@snu.ac.kr.