The peptide ghrelin is the endogenous ligand for the growth-hormone secretagogue receptor (GHSR-1a), also referred to as the ghrelin receptor. While the primary role of ghrelin relates to appetite regulation, there is increasing evidence for the cancer associated implications of the presence of the GHSR. We are developing a variety of fluorine-containing ghrelin analogues for the purpose of molecular imaging of the GHSR-1a and as potential diagnostic-therapeutic pairs. While natural 28-mer ghrelin (IC50 = 3.1 nM) has poor in vivo stability, we have developed ghrelin(1-8) analogues with fluorine-containing side-chains that have improved receptor affinity and serum stability. Modifications at positions 1, 3, 4, and 8 resulted in low MW octapeptides with receptor affinity superior to that of full length ghrelin (IC50 = 0.1 nM). Peptidomimetics containing fluorine, based upon the growth hormone secretagogue G-7039, have also been developed with sub-nanomolar GHSR-1a affinity. These ghrelin receptor targeting peptides and peptidomimetics have been successfully radiolabelled with 18F for PET imaging, while also having the potential to be used as peptide therapeutics with natural 19F.
Dr. Len Luyt received his Ph.D. from the University of Western Ontario in Chemistry and subsequently undertook a post-doctoral fellowship with Prof. John Katzenellenbogen at the University of Illinois, Urbana-Champaign. He then led a research team as a Senior Medicinal Chemist with the pharmaceutical company Bayer-Schering. Dr. Luyt joined Western University in 2005 as a faculty member with a joint appointment in the Departments of Oncology, Chemistry and Medical Imaging. He has published 40 journal articles, 5 book chapters, greater than 80 conference abstracts, and has 9 patents granted or applied for. He was awarded the Early Researcher Award (ERA) from the Ministry of Research and Innovation, the Vanguard award as Innovator of the year from Worldiscoveries, and has held peer-reviewed grant funding from NSERC, CIHR, OICR, Prostate Cancer Canada and the Canadian Breast Cancer Foundation. The research program of Dr. Luyt spans from basic chemistry activities, looking at novel methods of incorporating metal complexes into peptide structures, through to applied research, investigating new peptide therapeutics and molecular imaging agents for novel cancer targets.