Harnessing the potential of the THP: moving toward the development of a clinical-grade kit for a peptide-based PET imaging agent for real-time imaging of aberrant c-Met cancers for another giant step in cancer treatment

Principal investigator: Silvia Panseri

Personnel involved: Monica Montesi, Giada Bassi, Arianna Rossi, Mohamed Saqawa

Starting date: 16/10/2023
Duration: 24 months
Total funding: 261.437,00 €
Action: PRIN: PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE – Bando 2022
CNR-ISSMC role: Partner
Coordinator: Dr. Giuseppe Floresta – Università di Catania
Consortium: 4 partners (Università degli Studi di Catania Dr. Floresta; ISSMC-CNR Dr. Panseri; Università degli studi “Magna Grecia” di Catanzaro Dr. Procopio; Università degli studi di Firenze Dr. Crocetti).

Aberrant hepatocyte growth factor/hepatocyte growth factor receptor (HGFR or c-Met) signalling is involved in the development of several tumour types. Knowledge of c-Met expression in real-time will assist in the diagnosis and in the monitoring of response to therapy. The overall objective of the project is to evaluate/produce a library of molecular agents able to effectively target c-Met and to efficiently bind gallium-68 and/or iodine-124/131, and therefore to be exploited as c-Met PET imaging tracers as well as theragnostic purposes. The agent structure will therefore consist of a protein that will locate the tissues affected by the disease, and of particular units that will bind the radioelement and make the cells visible in the positron emission tomography. The expected results of the project are to select the most promising and effective tracers among the library of synthesized compounds for further preclinical and clinical development. The objective will be achieved thanks to a rational design and synthesis of the novel peptides-based PET tracers. The cellular interactions of already produced c-Met sequences will be studied and novel chemistry for a convenient covalent bind of iodine to hydroxypiridinones (the radioactively labelled part of the probes) will be developed and radioevaluated. It is logical to believe that, in future clinical practice, non-invasive PET imaging with the developed tracers will support not only the diagnosis of c-Met overexpressed cancers but also the selection of patients for c-Met–targeting drugs (Met inhibitors and anti-Met antibodies), as well as identifying responding and nonresponding patients for such therapeutic agents.