Site-selective radiolabeling of peptides by (18)F-fluorobenzoylation with [(18F)]SFB in solution and on solid phase: a comparative study.
Peptides labeled with short-lived positron-emitting radionuclides are of outstanding interest as probes for molecular imaging by positron emission tomography (PET). Herein, the site-selective incorporation of fluorine-18 into lysine-containing peptides using the prosthetic labeling agent N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB) is described. The reaction of [(18)F]SFB with four biologically relevant resin-bound peptides was studied and optimized. For comparison, each peptide was 18F-fluorobenzoylated in solution under different conditions and the product distribution was analyzed confirming the advantages of the solid-phase approach. The method's feasibility for selective radiolabeling either at the N-terminus or at the lysine side chain was demonstrated. Labeling on solid phase with [(18)F]SFB resulted in crude (18)F-fluorobenzoylpeptides whose radiochemical purities were typically greater than 90% and that could be prepared in synthesis times from 65 to 76 min.
Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany.
Manuela
M
Kuchar
Marc
M
Pretze
Torsten
T
Kniess
Jörg
J
Steinbach
Jens
J
Pietzsch
Reik
R
Löser
D001565:Benzoates / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D008239:Lysine / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D060327:Solid-Phase Synthesis Techniques / Q000379:methods; D012996:Solutions; D013388:Succinimides / Q000737:chemistry*
D001565:Benzoates; D005462:Fluorine Radioisotopes; D055767:Immobilized Proteins; D010455:Peptides; D019275:Radiopharmaceuticals; D012996:Solutions; D013388:Succinimides; C075713:N-succinimidyl-4-fluorobenzoate; D008239:Lysine