Systematic comparison of two novel, thiol-reactive prosthetic groups for F-18 labeling of peptides and proteins with the acylation agent succinimidyl-4-[F-18]fluorobenzoate ([F-18]SFB)

作者：Wuest Frank^*; Koehler Lena; Berndt Mathias; Pietzsch Jens

来源：Amino Acids, 2009, 36(2): 283-295.

DOI：10.1007/s00726-008-0065-2

• F-18-labeled prosthetic groups
• Peptides
• LDL
• Apolipoproteins
• Positron emission tomography (PET)

A systematic comparison of 4-[F-18]fluorobenzaldehyde-O-(2-{2-[2-(pyrrol-2,5-dione-1-yl)ethoxy]-ethoxy}-ethyl)oxime ([F-18]FBOM) and 4-[F-18]fluorobenzaldehyde-O-[6-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-hexyl]oxime ([F-18]FBAM) as prosthetic groups for the mild and efficient F-18 labeling of cysteine-containing peptides and proteins with the amine-group reactive acylation agent, succinimidyl-4-[F-18]fluorobenzoate ([F-18]SFB), is described. All three prosthetic groups were prepared in a remotely controlled synthesis module. Synthesis of [F-18]FBOM and [F-18]FBAM was accomplished via oxime formation through reaction of appropriate aminooxy-functionalized labeling precursors with 4-[F-18]fluorobenzaldehyde. The obtained radiochemical yields were 19% ([F-18]FBOM) and 29% ([F-18]FBAM), respectively. Radiolabeling involving [F-18]FBAM and [F-18]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 [F-18]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 [F-18]SFB. The obtained results demonstrate that [F-18]FBOM is especially suited for the labeling of hydrophilic cysteine-containing peptides, whereas [F-18]FBAM shows superior labeling performance for higher molecular weight compounds as exemplified for nLDL apolipoprotein constituents. However, the acylation agent [F-18]SFB is the preferred prosthetic group for labeling nLDL under physiological conditions.

• 出版日期2009-2