Recent progress in the imaging of c‐Met aberrant cancers with positron emission tomography

Abstract

Tyrosine‐protein kinase Met—also known as c‐Met or HGFR—is a membrane receptor protein with associated tyrosine kinase activity physiologically stimulated by its natural ligand, the hepatocyte growth factor (HGF), and is involved in different ways in cancer progression and tumourigenesis. Targeting c‐Met with pharmaceuticals has been preclinically proved to have significant benefits for cancer treatment. Recently, evaluating the protein status during and before c‐Met targeted therapy has been shown of relevant importance by different studies, demonstrating that there is a correlation between the status (e.g., aberrant activation and overexpression) of the HGFR with therapy response and clinical prognosis. Currently, clinical imaging based on positron emission tomography (PET) appears as one of the most promising tools for the in vivo real‐time scanning of irregular alterations of the tyrosine‐protein kinase Met and for the diagnosis of c‐Met related cancers. In this study, we review the recent progress in the imaging of c‐Met aberrant cancers with PET. Particular attention is directed on the development of PET probes with a range of different sizes (HGF, antibodies, anticalines, peptides, and small molecules), and radiolabeled with different radionuclides. The goal of this review is to report all the preclinical imaging studies based on PET imaging reported until now for in vivo diagnosis of c‐Met in oncology to support the design of novel and more effective PET probes for in vivo evaluation of c‐Met.

Peptide-based positron emission tomography probes: current strategies for synthesis and radiolabelling

“…In nuclear medicine research, gallium-68, DOTA-based chelators, and amino acid linkers are currently dominating the research of new potential diagnostic and imaging agents. 145 In centres, where 68 Ga-compounds cannot be used due to gallium unavailability, yttrium-86 or zirconium-89 are normally employed. All the other examples of radionuclides reported in this review are either in the preclinical or clinical research phase, and with this the review it is hoped to assist scientists in the field of peptide PET probe labelling by reporting all the cutting-edge technology that is currently available for the chemical modification of peptides in order to make them suitable for PET imaging.…”

Computer-Assisted Design of Peptide-Based Radiotracers

“…PET and SPECT imaging rely on the use of radioactive isotopes. To exploit these peptides as imaging or therapeutic agents, they must be covalently or non-covalently radiolabeled with selected radioactive isotopes [ 1 , 14 ].…”

“…This field of application is particularly relevant because of the rising global frequency of malignant tumors in the population. The interactions of the radiolabeled peptide-based probe with cancer cells are typically carried out through protein structures that are overexpressed in these malignant cells [ 14 , 15 , 16 , 17 , 18 , 19 ]. These radioactive isotopes can be attached to peptides to create imaging probes that bind to specific molecular targets in vivo.…”

Synthesis and preclinical evaluation of a selective MET kinase positron emission tomography tracer

“…Several strategies to image MET expression in vivo have been explored, predominantly using peptides or monoclonal antibodies 13,14 . For radiotracers based on small molecular weight compounds targeting the intracellular domain of MET, there is only a few reports so far 15–17 .…”