Abstract
Herein, we present a one-step labeling procedure of N-succinimidyl-4-[18F]-fluorobenzoate ([18F]SFB) starting from spirocyclic iodonium ylide precursors. Precursor syntheses succeeded via a simple one-pot, two-step synthesis sequence, in yields of approximately 25%. Subsequent 18F-nucleophilic aromatic labeling was performed, and radiochemical incorporations (RCCs) from 5–35% were observed. Purification could be carried out using HPLC and subsequent solid phase extraction. Radiochemical purity (RCP) of >95% was determined. The total synthesis time, including purification and formulation, was no longer than 60 min. In comparison to the established 3-step synthesis route of [18F]SFB, this one-step approach avoids formation of volatile radioactive side-products and simplifies automatization.
Highlights
N-succinimidyl-4-[18 F]fluorobenzoate ([18 F]SFB) is one of the most used prosthetic groups for labeling of proteins and peptides
[18 F]SFB has been successfully applied in the synthesis of inhibited factor VII [1], RGDs [4], or serum albumin [6]
Current synthesis approaches are routinely based on a 3-step synthesis sequence starting with an 18 F-aromatic nucleophilic substitution (SN Ar) of 4-(ethoxycarbonylphenyl)trimethylammonium triflate (1), followed by a hydrolysis step of the corresponding ethyl ester (2) to the benzoic acid derivative [18 F]3 ([18 F]FBA) and finalized by formation of [18 F]SFB (Figure 1) [1,2,3,4,5,6,7]
Summary
N-succinimidyl-4-[18 F]fluorobenzoate ([18 F]SFB) is one of the most used prosthetic groups for labeling of proteins and peptides. The 3-step synthesis of [18 F]SFB is further complicated since relatively high amounts of a volatile radioactive side-product, probably [18 F]FMe, are released [8]. This released side-product can limit the number of possible syntheses repetitions before permitted release levels are reached. In this respect, one-step, direct labeling conditions to synthesize [18 F]SFB are highly desirable. Reports conditions can usually not be translated to one-step procedures with similar radiochemical make use of aliquot labeling conditions that can usually not be translated to one-step incorporations (RCCs) or radiochemical yields (RCYs) [12].
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