Systematic comparison of two novel, thiol-reactive prosthetic groups for 18F labeling of peptides and proteins with the acylation agent succinimidyl-4-[18F]fluorobenzoate ([18F]SFB).
A systematic comparison of 4-[18F]fluorobenzaldehyde-O-(2-{2-[2-(pyrrol-2,5-dione-1-yl)ethoxy]-ethoxy}-ethyl)oxime ([18F]FBOM) and 4-[18F]fluorobenzaldehyde-O-[6-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-hexyl]oxime ([18F]FBAM) as prosthetic groups for the mild and efficient 18F labeling of cysteine-containing peptides and proteins with the amine-group reactive acylation agent, succinimidyl-4-[18F]fluorobenzoate ([18F]SFB), is described. All three prosthetic groups were prepared in a remotely controlled synthesis module. Synthesis of [18F]FBOM and [18F]FBAM was accomplished via oxime formation through reaction of appropriate aminooxy-functionalized labeling precursors with 4-[18F]fluorobenzaldehyde. The obtained radiochemical yields were 19% ([18F]FBOM) and 29% ([18F]FBAM), respectively. Radiolabeling involving [18F]FBAM and [18F]FBOM was exemplified by the reaction with cysteine-containing tripeptide glutathione (GSH), a cysteine-containing dimeric neurotensin derivative, and human native low-density lipoprotein (nLDL) as model compounds. Radiolabeling with the acylation agent [18F]SFB was carried out using a dimeric neurotensin derivative and nLDL. Both thiol-group reactive prosthetic groups show significantly better labeling efficiencies for the peptides in comparison with the acylation agent [18F]SFB. The obtained results demonstrate that [18F]FBOM is especially suited for the labeling of hydrophilic cysteine-containing peptides, whereas [18F]FBAM shows superior labeling performance for higher molecular weight compounds as exemplified for nLDL apolipoprotein constituents. However, the acylation agent [18F]SFB is the preferred prosthetic group for labeling nLDL under physiological conditions.
Wuest
Frank
F
Research Center Dresden-Rossendorf, Institute for Radiopharmacy, PF 510 119, 01314 Dresden, Germany. f.wuest@fzd.de
Köhler
Lena
L
Berndt
Mathias
M
Pietzsch
Jens
J
D000215:Acylation; D001565:Benzoates / Q000737:chemistry*; D008078:Cholesterol, LDL / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008301:Maleimides / Q000737:chemistry*; D009496:Neurotensin / Q000737:chemistry; D010091:Oximes / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry*; D013388:Succinimides / Q000737:chemistry*
C539753:4-fluorobenzaldehyde-O-(2-(2-(2-(pyrrol-2,5-dione-1-yl)ethoxy)ethoxy)ethyl)oxime; D001565:Benzoates; D008078:Cholesterol, LDL; D005462:Fluorine Radioisotopes; D008301:Maleimides; C518594:N-(6-(4-fluorobenzylidene)aminooxyhexyl)maleimide; D010091:Oximes; D010455:Peptides; D011506:Proteins; D019275:Radiopharmaceuticals; D013388:Succinimides; C075713:N-succinimidyl-4-fluorobenzoate; D009496:Neurotensin