Analysis of progress and challenges for various patterns of c-MET-targeted molecular imaging: a systematic review

Abstract

BackgroundMesenchymal–epithelial transition factor also named c-MET is a receptor tyrosine kinase for the hepatocyte growth factor that plays a pivotal role in tumorigenesis. c-MET-targeted therapies have been tested in preclinical models and patients, with significant benefits for cancer treatment. In recent years, many studies have shown that the expression level and activation status of c-MET are closely correlated to c-MET-targeted therapy response and clinical prognosis, thus highlighting the importance of evaluating the c-MET status during and prior to targeted therapy. Molecular imaging allows the monitoring of abnormal alterations of c-MET in real time and in vivo.ResultsIn this review, we initially summarize the recent advances in c-MET-targeted molecular imaging, with a special focus on the development of imaging agents ranging in size from monoclonal antibody to small molecule. The aim of this review is to report the preclinical results and clinical application of all molecular imaging studies completed until now for in vivo detection of c-MET in cancer, in order to be beneficial to development of molecular probe and the combination of molecular imaging technologies for in vivo evaluation of c-MET. Various molecular probe targeted to c-MET possesses distinctive advantages and disadvantages. For example, antibody-based probes have high binding affinity but with long metabolic cycle as well as remarkable immunogenicity.ConclusionsAlthough studies for c-MET-targeted molecular imaging have made many important advances, most of imaging agents specifically target to extracellular area of c-MET receptor; however, it is difficult to reflect entirely activation of c-MET. Therefore, small molecule probes based on tyrosine kinase inhibitors, which could target to intracellular area of c-MET without any immunogenicity, should be paid more attention.

Preliminary application of micro‐SPECT/CT imaging by 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met for non‐small‐cell lung cancer

“…Over decades, c‐Met has increasingly been utilized as a biomarker for molecular imaging. Various c‐Met‐targeted imaging agents have been developed based on the HGF ligand, antibodies, peptides, genetically encoded proteins, anticalins, and small molecules (Han et al., ). Evidently, whether it is a HGF ligand, antibody, peptide, or small molecule has unique advantages and disadvantages.…”

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

“…Due to a limited number of validated MET mAbs that work in formalin-fixed and paraffin embedded biopsy samples, immunohistochemical evaluation of MET expression is a challenge [ 282 ]. Since HGF has been recognized to have a high binding affinity and specificity to MET, initial studies on targeted molecular imaging of MET were therefore mainly based on HGF ligands [ 283 ]. The recombinant human HGF was [ 64 Cu]-labeled ([ 64 Cu]Cu-rh-HGF) and PET imaging revealed specific and prominent uptake of the radiopharmaceutical in MET positive U87MG GB tumors [ 284 ].…”

“…The recombinant human HGF was [ 64 Cu]-labeled ([ 64 Cu]Cu-rh-HGF) and PET imaging revealed specific and prominent uptake of the radiopharmaceutical in MET positive U87MG GB tumors [ 284 ]. One concern for these radiopharmaceuticals based on the HGF ligand is their potential to stimulate tumor growth by activating c-met and competition with the endogenous ligand, hindering clinical translation [ 27 , 283 , 284 ]. Hence, the mAb-based PET radiopharmaceuticals [ 89 Zr]Zr-onartuzumab and [ 76 Br]Br-onartuzumab were developed that specifically target MET in vitro and in vivo.…”

Synthesis and Preclinical Evaluation of [18F]PF04217903, a Selective MET PET Tracer

“…11 Several strategies to image MET expression in vivo has been explored, predominantly using peptides or monoclonal antibodies. 13 For radiotracers based on small molecular weight compounds targeting the intracellular domain of MET, there is so far only one report. 14 As therapeutic PKIs bind intracellularly, radiotracers binding to the same active site may be important to properly asses target expression and engagement.…”