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Peptidomimetic growth hormone secretagogue derivatives for positron emission tomography imaging of the ghrelin receptor.
Fowkes, Milan M; Lalonde, Tyler; Yu, Lihai; Dhanvantari, Savita; Kovacs, Michael S; Luyt, Leonard G.
Afiliación
  • Fowkes MM; Department of Chemistry, Western University, 1151 Richmond Street, London, Ontario, N6A 5B7, Canada; London Regional Cancer Program, Lawson Health Research Institute, 790 Commissioners Road East, London, Ontario, N6A 4L6, Canada.
  • Lalonde T; Department of Chemistry, Western University, 1151 Richmond Street, London, Ontario, N6A 5B7, Canada; London Regional Cancer Program, Lawson Health Research Institute, 790 Commissioners Road East, London, Ontario, N6A 4L6, Canada.
  • Yu L; Department of Chemistry, Western University, 1151 Richmond Street, London, Ontario, N6A 5B7, Canada; London Regional Cancer Program, Lawson Health Research Institute, 790 Commissioners Road East, London, Ontario, N6A 4L6, Canada.
  • Dhanvantari S; Imaging Program, Lawson Health Research Institute, 268 Grosvenor Street, London, Ontario, N6A 4V2, Canada.
  • Kovacs MS; Imaging Program, Lawson Health Research Institute, 268 Grosvenor Street, London, Ontario, N6A 4V2, Canada.
  • Luyt LG; Department of Chemistry, Western University, 1151 Richmond Street, London, Ontario, N6A 5B7, Canada; London Regional Cancer Program, Lawson Health Research Institute, 790 Commissioners Road East, London, Ontario, N6A 4L6, Canada; Imaging Program, Lawson Health Research Institute, 268 Grosvenor Stree
Eur J Med Chem ; 157: 1500-1511, 2018 Sep 05.
Article en En | MEDLINE | ID: mdl-30282322
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hormona del Crecimiento / Tomografía de Emisión de Positrones / Receptores de Ghrelina / Peptidomiméticos Límite: Humans Idioma: En Revista: Eur J Med Chem Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Francia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hormona del Crecimiento / Tomografía de Emisión de Positrones / Receptores de Ghrelina / Peptidomiméticos Límite: Humans Idioma: En Revista: Eur J Med Chem Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Francia