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Synthesis of N-succinimidyl 4-[18F]fluorobenzoate, an agent for labeling proteins and peptides with 18F

Abstract

This protocol describes the step-by-step procedure for the synthesis of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB), an agent widely used for labeling proteins and peptides with the positron-emitting radionuclide 18F. The protocols for the synthesis of unlabeled SFB and the quaternary salt precursor 4-formyl-N,N,N-trimethyl benzenaminium trifluoromethane sulfonate also are described. For the [18F]SFB synthesis, the quaternary salt is first converted to 4-[18F]fluorobenzaldehyde. Oxidation of the latter provides 4-[18F]fluorobenzoic acid, which is converted to [18F]SFB by treatment with N,N-disuccinimidyl carbonate. Using this method, [18F]SFB can be synthesized in decay-corrected radiochemical yields of 30%–35% and a specific radioactivity of 11–12 GBq μmol−1. The total synthesis and purification time required is about 80 min, starting from delivery of the [18F]fluoride. [18F]SFB remains an optimal reagent for labeling proteins and peptides with 18F because of good conjugation yields and metabolic stability.

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Figure 1: Scheme for the synthesis of N-succinimidyl 4-[18F]fluorobenzoate.
Figure 2

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Acknowledgements

This work was supported by grants from US Department of Energy and the US National Institutes of Health.

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G.V. conceived the idea, designed and executed the experiments and contributed to the writing of the paper. M.R.Z. provided financial support and contributed to the writing of the paper.

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Correspondence to Ganesan Vaidyanathan or Michael R Zalutsky.

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Vaidyanathan, G., Zalutsky, M. Synthesis of N-succinimidyl 4-[18F]fluorobenzoate, an agent for labeling proteins and peptides with 18F. Nat Protoc 1, 1655–1661 (2006). https://doi.org/10.1038/nprot.2006.264

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