DEVELOPMENT OF NEW RADIOTRACERS FOR THE MOLECULAR IMAGING OF EGFR AND CCK2 R OVEREXPRESSING TUMORS

Nuclear imaging is one of the fastest-growing areas of medical imaging. It is used for early detection, characterization, and “real-time” monitoring of disease as well as investigating the efficacy of drugs. This is possible thanks to special high-sensitive techniques such as radionuclide-based positron emission tomography (PET) and single photon emission computed tomography (SPECT), which can determine concentrations of specific biomolecules as low as in the picomolar range. One of the significant benefits provided by imaging techniques is the ability to gather biological information at the cellular, subcellular, and molecular levels within living subjects through non-invasive procedures. This diagnostic procedure is possible by developing radiolabeled molecules able to specifically recognize peculiar targets characterizing the disease like overexpressed receptors or variations of metabolic pathways. Some attractive biological targets are the epidermal grow factor receptor (EGFR), a member of the receptors tyrosine kinases (RTKs) group, and cholecystokinin-2 receptor (CCK2-R), a GPCR belonging to the cholecystokinin receptor (CCKR) family. Many works in literature have reported overexpression of these receptors in multiple cancer types such as glioblastoma, lung, breast, colorectal, and oral cancers for EGFR, and gastric adenocarcinomas, medullary thyroid carcinoma, and pancreatic tumors for CCK2-R. For this reason, EGFR and CCK2-R are good candidates for the development of new tracers for imaging studies. Herein we present the development and the preliminary biological evaluation of two distinct series of radiotracers: 1. 18F-labeled small molecules for the imaging of EGFR overexpressing cancers. 2. 64Cu/68Ga-labeled saccharidic ligands for the imaging of CCK2-R overexpressing cancers. Besides, the synthesis and biological evaluation of fluorescent saccharidic probes for targeting CCK2-R are reported.