The Design and Synthesis of Molecular Imaging Probes Using A Novel Peptide Hormone Ghrelin

Ghrelin is a 28-amino acid peptide hormone that was first discovered in 1999 by Kojima et al. Recently, we have developed molecular imaging agents using ghrelin analogues that selectively target the growth hormone secretagogue receptor la (GHSR- la). This is accomplished by placing the imaging component at either the C-terminus of the peptide through a pendant lysine side-chain, or through modification of the Ser-3 residue. Receptor binding assays confirmed that fluorescein ghrelin(l-18) (IC50 = 9.5 nM) and non-radioactive fluorine and gallium containing ghrelin analogues (IC50 = 2.88 - 65 nM) bound to the GHSR-la with high affinity. Fluorescein ghrelin(l-18) demonstrated high uptake in the human prostate cancer cell lines PC-3 and LNCaP, as well as ex vivo human prostate cancer tissue. This work supported the development of a radiolabelling strategy for incorporating gallium-68 and fluorine-18 into modified ghrelin, for use in PET nuclear imaging