Development of a [68Ga]-ghrelin analogue for PET imaging of the ghrelin receptor (GHS-R1a)

C. L. Charron; M. S. McFarland; S. Dhanvantari; L. G. Luyt

doi:10.1039/C8MD00210J

Development of a [⁶⁸Ga]-ghrelin analogue for PET imaging of the ghrelin receptor (GHS-R1a)†

C. L. Charron,^a M. S. McFarland,^a S. Dhanvantari

^bc and L. G. Luyt

*^ade

Author affiliations

* Corresponding authors

^a Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B7, Canada
E-mail: lluyt@uwo.ca

^b Lawson Health Research Institute, 268 Grosvenor Street, London, Ontario N6A 4V2, Canada

^c Departments of Medical Biophysics, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B7, Canada

^d Department of Oncology, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B7, Canada

^e London Regional Cancer Program, Lawson Health Research Institute, 800 Commissioners Road East, London, Ontario N6A 5W9, Canada

Abstract

The ghrelin receptor is a member of the growth hormone secretagogue receptor (GHS-R) family and is present at low concentrations in tissues such as the brain, kidney, cardiovascular system, and prostate. The ghrelin receptor plays an important role in cellular proliferation, apoptosis, invasion, and migration associated with the progression of many cancers, including prostate, breast, ovarian, testicular, and intestinal carcinomas. Ghrelin, the endogenous ligand, is a 28 amino acid peptide (IC₅₀ = 3.1 nM) known to have poor in vivo stability. Herein, we report the synthesis and evaluation of [Dpr³(octanoyl),Lys¹⁹(Ga-DOTA)]ghrelin(1-19). This new ghrelin analogue has a binding affinity (IC₅₀ = 5.9 nM) comparable to that of natural ghrelin. Preliminary in vivo evaluation shows higher uptake of [Dpr³(octanoyl),Lys¹⁹(⁶⁸Ga-DOTA)]ghrelin(1-19) in HT1080/GHSR-1a xenografts than the non-transfected HT1080 xenografts in NOD-SCID mice, although considerable uptake is observed in the kidneys. This is the first example of ghrelin receptor PET imaging in a xenograft model using a peptide derived directly from the endogenous ligand and serves as motivation for developing more effective ghrelin-based radiopeptides.

This article is part of the themed collection: Molecular Pharmacology

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Article information

DOI: https://doi.org/10.1039/C8MD00210J
Article type: Research Article
Submitted: 18 Apr 2018
Accepted: 09 Sep 2018
First published: 17 Sep 2018

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Med. Chem. Commun., 2018,9, 1761-1767

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Development of a [⁶⁸Ga]-ghrelin analogue for PET imaging of the ghrelin receptor (GHS-R1a)

C. L. Charron, M. S. McFarland, S. Dhanvantari and L. G. Luyt, Med. Chem. Commun., 2018, 9, 1761 DOI: 10.1039/C8MD00210J

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