A phase 2 liver trial where the add-on drug didn't help — and the base drug quietly did
Read the Sunday Brief →

Study wrapper · #193

Peptidomimetic growth hormone secretagogue derivatives for positron emission tomography imaging of the ghrelin receptor.

Fowkes MM, Lalonde T, Yu L, et al. European journal of medicinal chemistry. 2018.

Editor's note

A medicinal-chemistry, in-vitro study developing peptide-based PET imaging probes that target the ghrelin receptor, which is overexpressed in some cancers and in heart failure. This is early laboratory and radiochemistry work, not a therapeutic or clinical study, and ipamorelin appears here only as one of several scaffolds tested for attaching a fluorine-18 label, not as a treatment. The relevance to our readers is therefore mechanistic and indirect: it illustrates that ipamorelin and related growth-hormone secretagogues bind the ghrelin receptor tightly enough to serve as targeting backbones for imaging agents. Researchers reported that among the peptidic and peptidomimetic candidates, a compound called G-7039 was best suited to radiolabelling, with high binding affinity and in-vitro potency, and that the resulting fluorine-18 probe was produced at high radiochemical purity. No animal or human imaging data are reported. This is a proof-of-concept chemistry result showing a candidate diagnostic probe worth further investigation; it says nothing about ipamorelin's effects in the body. These are in-vitro findings; in-vivo and human data would be needed before diagnostic conclusions.

Plain-language abstract

This was a laboratory chemistry study, not a study of treatment or of effects in people or animals. Its goal was to design a scanning agent for PET imaging, a type of medical scan, that could locate the ghrelin receptor, which is present at higher-than-normal levels on some cancer cells and in heart failure. The researchers built several small peptide-based molecules based on known ghrelin-receptor binders, including GHRP-1, GHRP-2, GHRP-6, ipamorelin and a molecule called G-7039, and tested where a radioactive fluorine label could best be attached without harming the molecule's ability to bind the receptor. Ipamorelin was used here purely as one of several molecular building blocks, not as a drug. Among the candidates, G-7039 worked best: it bound the target tightly and was potent in cell tests, and a version carrying radioactive fluorine-18 was made at very high purity. The authors suggested this compound could be studied further as a PET scanning probe to detect diseases marked by too many ghrelin receptors. No animal or human scans were reported, so further testing would be needed.