Investigation of Fluorine-18 Labelled Peptides for Binding to Cholecystokinin-2 Receptors with High Affinity

Abstract Many cancers of neuroendocrine origin overexpress cholecystokinin-2 receptors (CCK-2R) including medullary thyroid cancer, small cell lung cancer and other carcinoids. Fluorine-18 labelled peptides targeting CCK-2R enable direct visualization quantification this receptor in vivo using positron emission tomography imaging. CP04 1 MG11 2 are two previously described truncated derived from the native hormone ligand, gastrin. The N -terminus octopeptide was chemically modified with various fluorine containing aromatic (4-fluorobenzoate), heterocyclic (6-fluoronicotinate) aliphatic (2-fluoropropionate) moieties. To assess impact these modifications had on binding, ligand-binding assays were conducted A431 cells overexpressing human CCK-2R. by 4-fluorobenzoate (FB-MG11 3 ) demonstrated highest binding affinity (0.20 nM) followed 6-fluoronicotinate (FNic-MG11 4 ; 0.74 2-fluoropropionate (FP-MG11 5 1.80 nM), respectively. Whilst indirect labelling fluorine-18 activated esters fluorobenzoate unsuccessful, at 6-nitronicotinate afforded a 47.6% radiochemical yield [ 18 F]FNic-MG11. Unfortunately, F]FNic-MG11 unstable, decomposing slowly through defluorination, thereby impeding any further work radiotracer.