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Radiofluorination of non-activated aromatic prosthetic groups for synthesis and evaluation of fluorine-18 labelled ghrelin(1-8) analogues.
Childs, Marina D; Yu, Lihai; Kovacs, Michael S; Luyt, Leonard G.
Afiliación
  • Childs MD; Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 3 K7, Canada. lluyt@uwo.ca.
  • Yu L; London Regional Cancer Program, Lawson Health Research Institute, 800 Commissioners Road East, London, Ontario, N6A 4L6, Canada.
  • Kovacs MS; Department of Medical Imaging, University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 3 K7, Canada.
  • Luyt LG; Department of Medical Biophysics, University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 3 K7, Canada.
Org Biomol Chem ; 19(40): 8812-8820, 2021 10 20.
Article en En | MEDLINE | ID: mdl-34590643
The growth hormone secretagogue receptor 1a (GHSR) is differentially expressed in various disease states compared to healthy tissues and thus is a target for molecular imaging. The endogenous ligand for the GHSR is ghrelin, a 28 amino acid peptide with a unique octanoyl group on the serine-3 residue. A recently reported ghrelin analogue revealed the successful use of fluorine-containing, polycyclic aromatic groups in place of the octanoyl side chain, thereby providing potential access to new 18F-PET imaging probes. The peptide [Inp1,Dpr3(6-FN),1Nal4,Thr8]ghrelin(1-8) amide (1) showed sub-nanomolar receptor affinity (IC50 = 0.11 nM) toward the GHSR making it the strongest affinity ghrelin analogue reported to date. However, attempts to label such non-activated aromatic groups with fluoride-18 through conventional substitution methods resulted in low radiochemical yields, impractical for use in vivo. Since larger, non-activated aromatic groups appear to be of value for incorporating fluorine into ghrelin(1-8) analogues, an additional peptide bearing a 4'-fluorobiphenyl-4-carboxyl (4'-FBC) group in place of the octanoyl side chain was also of interest. Herein, we describe the radiosynthesis of [Inp1,Dpr3([18F]6-FN),1Nal4,Thr8]ghrelin(1-8) amide ([18F]1) and [Inp1,Dpr3([18F]4'-FBC),1Nal4,Thr8]ghrelin(1-8) amide ([18F]2) using a prosthetic group approach from iodonium ylide precursors as well as initial in vitro and in vivo evaluation of [18F]1 as a potential PET tracer for targeted imaging of the GHSR.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Radioisótopos de Flúor Idioma: En Revista: Org Biomol Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Radioisótopos de Flúor Idioma: En Revista: Org Biomol Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido