Synthesis and evaluation of 18F labeled crizotinib derivative [18F]FPC as a novel PET probe for imaging c-MET-positive NSCLC tumor

Qingyu Lin; Yingying Zhang; Zhequan Fu; Bingxin Hu; Zhan Si; Yanzhao Zhao; Hongcheng Shi; Dengfeng Cheng

doi:10.1016/j.bmc.2020.115577

Synthesis and evaluation of ¹⁸F labeled crizotinib derivative [¹⁸F]FPC as a novel PET probe for imaging c-MET-positive NSCLC tumor

Bioorg Med Chem. 2020 Aug 1;28(15):115577. doi: 10.1016/j.bmc.2020.115577. Epub 2020 May 30.

Authors

Qingyu Lin¹, Yingying Zhang², Zhequan Fu², Bingxin Hu², Zhan Si², Yanzhao Zhao², Hongcheng Shi³, Dengfeng Cheng⁴

Affiliations

¹ Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Nuclear Medicine, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China.
² Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
³ Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Nuclear Medicine, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China. Electronic address: shi.hongcheng@zs-hospital.sh.cn.
⁴ Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Nuclear Medicine, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China. Electronic address: cheng.dengfeng@zs-hospital.sh.cn.

PMID: 32631560
DOI: 10.1016/j.bmc.2020.115577

Abstract

c-MET-positive NSCLC is an important subtype accounting for about 5%~22% of lung cancer. NSCLC patients with activating c-MET are intensively sensitive to c-MET selective receptor tyrosine kinase (RTK) inhibitors, so we aimed to develop a specific PET probe targeting to c-MET-positive NSCLC for potential patients screened by PET/CT. Herein, PET tracer ¹⁸F-radiolabeled crizotinib derivative ([¹⁸F]FPC) was successfully achieved through a simple one-step ¹⁸F-labeling method. [¹⁸F]FPC PET imaging on c-MET-positive (as well as blocking group) and negative NSCLC models were further evaluated, and results showed that [¹⁸F]FPC was effective as a PET imaging probe that targeted c-MET-positive tumor. Therefore, [¹⁸F]FPC could be a potential PET imaging probe for NSCLC tumor which was sensitive to c-MET-TKIs. By virtue of this property, it will benefit NSCLC patients for c-MET-TKI treatment.

Keywords: Cellular-mesenchymal to epithelial transition factor (c-MET); Crizotinib; Non-small-cell lung carcinoma (NSCLC); Positron emission tomography (PET); [(18)F]FPC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
Carcinoma, Non-Small-Cell Lung / metabolism
Cell Line, Tumor
Contrast Media / chemical synthesis
Contrast Media / chemistry*
Contrast Media / pharmacokinetics
Crizotinib / analogs & derivatives*
Crizotinib / chemical synthesis
Crizotinib / pharmacokinetics
Fluorine Radioisotopes / chemistry
Humans
Male
Mice, Inbred BALB C
Positron-Emission Tomography
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacokinetics
Proto-Oncogene Proteins c-met / antagonists & inhibitors
Proto-Oncogene Proteins c-met / metabolism*
Radiopharmaceuticals / chemical synthesis
Radiopharmaceuticals / chemistry*
Radiopharmaceuticals / pharmacokinetics
Tissue Distribution

Substances

Contrast Media
Fluorine Radioisotopes
Protein Kinase Inhibitors
Radiopharmaceuticals
Crizotinib
MET protein, human
Proto-Oncogene Proteins c-met
Fluorine-18