Studies of drug resistance and micro-metastasis using macrocyclic peptides as molecular imaging probes

2017 Fiscal Year Final Research Report

• Project/Area Number: 16H06830
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Respiratory surgery
• Research Institution: Kanazawa University
• Principal Investigator: Hiroki Sato 金沢大学, がん進展制御研究所, 特任助教 (20781173)
• Co-Investigator(Renkei-kenkyūsha): MUKAI Hidefumi 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, ユニットリーダー (60570885)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Keywords: HGF / MET / イメージング / 薬剤耐性 / 環状ペプチド

Outline of Final Research Achievements

Activation of HGF-MET signaling causes resistance to molecular targeted drugs. Biomarkers that reflect expression levels and activation status for HGF-MET pathway are potentially be useful for diagnosis and better treatment of patients. In this study, we attempted to visualize for HGF-MET activation state with the PET imaging by using cyclic peptides which specifically bind to HGF or MET. In PET analysis, Cu-64-labeled HGF binder accumulated in HGF-overexpressing cancer xenografts at higher levels than those in parental xenografts in humanized mouse model. In MET-binding cyclic peptides, we evaluated cellular accumulation of MET probes following MET activation in relation to their chemical properties. Therefore, our results suggest that the novel imaging probes may become valuable companion diagnostic tools to evaluate activation status of HGF-MET pathway for patient selection for drug development and treatment.

Free Research Field

細胞生物学