title: Sulfonation of Tyrosine as a Method To Improve Biodistribution of Peptide-Based Radiotracers: Novel18F-Labeled Cyclic RGD Analogues.
abstract: Control of the biodistribution of radiolabeled peptides has proven to be a major challenge in their application as imaging agents for positron emission tomography (PET). Modification of peptide hydrophilicity in order to increase renal clearance has been a common endeavor to improve overall biodistribution. Herein, we examine the effect of site-specific sulfonation of tyrosine moieties in cyclic(RGDyK) peptides as a means to enhance their hydrophilicity and improve their biodistribution. The novel sulfonated cyclic(RGDyK) peptides were conjugated directly to 4-nitrophenyl 2-[18F]fluoropropionate, and the biodistribution of the radiolabeled peptides was compared with that of their nonsulfonated, clinically relevant counterparts, [18F]GalactoRGD and [18F]FPPRGD2. Site-specific sulfonation of the tyrosine residues was shown to increase hydrophilicity and improve biodistribution of the RGD peptides, despite contributing just 79 Da toward the MW, compared with 189 Da for both the "Galacto" and mini-PEG moieties, suggesting this may be a broadly applicable approach to enhancing biodistribution of radiolabeled peptides.
authors.affiliation: The Centre for Molecular Imaging and Translational Research Laboratory, The Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia.
authors.forename: Mohammad B
authors.initials: MB
authors.lastname: Haskali
authors.affiliation: The Centre for Molecular Imaging and Translational Research Laboratory, The Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia.
authors.forename: Delphine
authors.initials: D
authors.lastname: Denoyer
authors.affiliation: The Centre for Molecular Imaging and Translational Research Laboratory, The Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia.
authors.forename: Wayne
authors.initials: W
authors.lastname: Noonan
authors.affiliation: The Centre for Molecular Imaging and Translational Research Laboratory, The Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia.
authors.forename: Carleen
authors.initials: C
authors.lastname: Culinane
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Rangger
authors.affiliation: The Centre for Molecular Imaging and Translational Research Laboratory, The Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia.
authors.forename: Normand
authors.initials: N
authors.lastname: Pouliot
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck , Innsbruck, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Haubner
authors.affiliation: The Centre for Molecular Imaging and Translational Research Laboratory, The Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Roselt
authors.affiliation: The Centre for Molecular Imaging and Translational Research Laboratory, The Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.forename: Craig A
authors.identifier: 0000-0002-2353-9258
authors.initials: CA
authors.lastname: Hutton
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D009596:Nitrophenols / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D009596:Nitrophenols; D010455:Peptides; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C507169:cyclic arginine-glycine-aspartic acid peptide; C024719:4-nitrophenyl; D014443:Tyrosine
keywords: PET imaging; RGD peptides; biodistribution; fluorine-18; sulfonation; tyrosine; tyrosine-3-sulfonate