Scientists made a special version of a ghrelin‑like peptide that can be tagged with a radioactive label for PET scans, aiming to see where the ghrelin receptor is over‑active in diseases like cancer or heart failure. The best candidate was a peptidomimetic called G‑7039, which showed good binding and could be labeled efficiently, but the work is focused on imaging, not on using the peptide to boost growth hormone or performance.

The ghrelin receptor is a seven-transmembrane (7-TM) receptor known to have an increased level of expression in human carcinoma and heart failure. Recent work has focused on the synthesis of positron emission tomography (PET) probes designed to target and image this receptor for disease diagnosis and staging. However, these probes have been restricted to small-molecule quinalizonones and peptide derivatives of the endogenous ligand ghrelin. We describe the design, synthesis and biological evaluation of a series of 4-fluorobenzoylated growth hormone secretagogues (GHSs) derived from peptidic (GHRP-1, GHPR-2 and GHRP-6) and peptidomimetic (G-7039, [1-Nal⁴]G-7039 and ipamorelin) families in order to test locations for the insertion of fluorine-18 for PET imaging. The peptidomimetic G-7039 was found to be the most suitable for ¹⁸F-radiolabelling as its non-radioactive 4-fluorobenzoylated analogue ([1-Nal⁴,Lys⁵(4-FB)]G-7039), had both a high binding affinity (IC₅₀ = 69 nM) and promising in vitro efficacy (EC₅₀ = 1.1 nM). Prosthetic group radiolabelling of the precursor compound [1-Nal⁴]G-7039 using N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) delivered the PET probe [1-Nal⁴,Lys⁵(4-[¹⁸F]-FB)]G-7039 in an average decay-corrected radiochemical yield of 48%, a radio-purity ≥ 99% and an average molar activity of >34 GBq/μmol. This compound could be investigated as a PET probe for the detection of diseases that are characterised by overexpression of the ghrelin receptor.