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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)

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Abstract

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.

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Acknowledgments

The authors are grateful to Mareike Barth, Stephan Preusche, and Tilow Krauss for their excellent technical assistance. Contributions of Christina Hultsch (Ph.D. thesis, University of Technology, Dresden, Germany) and Uta Schwietzke (diploma thesis at University of Technology, Dresden, Germany) are greatly acknowledged. We are also grateful to Sigrid Nitzsche (Lipoprotein Laboratory, Department of Internal Medicine 3, Carl Gustav Carus Medical School, University of Technology, Dresden) for her expert technical assistance with human LDL preparation and characterization. This work was partially supported by a grant from the Deutsche Forschungsgemeinschaft (DFG; grant no. PI304/1-1).

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  1. Research Center Dresden-Rossendorf, Institute for Radiopharmacy, PF 510 119, 01314, Dresden, Germany

    Frank Wuest, Lena Köhler, Mathias Berndt & Jens Pietzsch

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  1. Frank Wuest
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Correspondence to Frank Wuest.

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Wuest, F., Köhler, L., Berndt, M. et al. 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). Amino Acids 36, 283–295 (2009). https://doi.org/10.1007/s00726-008-0065-2

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