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Sulfonation of tyrosine as a method to improve biodistribution of peptide-based radiotracers: novel (18)F-labeled cyclic RGD analogues

journal contribution
posted on 2017-04-03, 00:00 authored by M B Haskali, Delphine Denoyer, W Noonan, C Culinane, C Rangger, N Pouliot, R Haubner, P D Roselt, R J Hicks, C A Hutton
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-[(18)F]fluoropropionate, and the biodistribution of the radiolabeled peptides was compared with that of their nonsulfonated, clinically relevant counterparts, [(18)F]GalactoRGD and [(18)F]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.

History

Journal

Molecular pharmaceutics

Volume

14

Issue

4

Pagination

1169 - 1180

Publisher

American Chemical Society

Location

Washington, D.C.

ISSN

1543-8384

eISSN

1543-8392

Language

eng

Publication classification

C Journal article; C1.1 Refereed article in a scholarly journal

Copyright notice

2017, American Chemical Society