Imaging of c-Met aberrant cancers with Gallium-68 chelators for positron emission tomography

c-Met is a receptor tyrosine kinase which, after activation by its ligand, the hepatocyte growth factor (HGF), mediates a range of intracellular signalling pathways including some related to proliferation, motility, migration and invasion of cancer cells. Aberrant HGF/c-Met signalling is involved in the development and metastatic progression of several tumour types. Thus, this protein receptor is a key player in cancer initiation and progression. For this reason, monitoring of c-Met expression in real time is likely to assist in the diagnosis and the monitoring of response to therapy. Positron emission tomography (PET) imaging represents one of the most promising clinical tools for the in vivo real-time monitoring of abnormal alterations of c-Met and for the diagnosis of c-Met related cancers. Here we present the rational design and synthesis of a library of novel peptide-chelator bioconjugates potentially able to effectively target c-Met and to efficiently bind gallium-68, and therefore to make the cells visible in the positron emission tomography. In fact, the main feature of ⁶⁸Ga is that it undergoes a spontaneous radioactive decay and releasing a positron, which is then measured by common hospital PET scanner. Moreover, the use of ⁶⁸Ga as radioactive species would abolish the costly infrastructures related with ¹⁸F and ¹¹C production and the more complex synthetic chemistry procedures involved in radiolabeling. Non-invasive PET imaging with the developed tracers will support powerful tools for the detection and monitoring of the most common and lethal cancers among Europe and worldwide.