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 micromol(-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.

N-(4-18F-Fluorobenzoyl)Interleukin-2 for PET of Human-Activated T Lymphocytes

“…N-succinimidyl 4-18 F-fluorobenzoate ( 18 F-SFB) was shown to be a suitable synthon for radiolabeling of peptides and proteins (9,10). 18 F-SFB is an activated ester that can be linked to lysine residues in the protein via an acylation reaction.…”

Protein and Antibody Functionalization Using Continuous Flow Microreactor Technology

“…As a first proof-of-principle study, N-succinimidyl-4-fluorobenzoate (FSB, 1) was conjugated to specimen protein standards using conventional and flow-mediated conditions. Reagent 1 was selected as in 18 F-labelled form it has applications in positron emission tomography (PET) imaging [7] allowing real-time biodistribution of conjugates to be monitored in vivo. The standards utilized included serum albumins, insulin, interferon, and myoglobin and were carried out under various reaction conditions probing time, temperature, and the role of base triethylamine (TEA) (Scheme 1 and Table 1).…”

Synthesis and In Vivo Evaluation ofp-18F-Fluorohippurate as a New Radiopharmaceutical for Assessment of Renal Function by PET

“…In this article, we present our preclinical work toward the development of an 18 F-based renal imaging radiopharmaceutical, the biologic properties of which (compared with 99m Tc-MAG3) may be closer to 131 I-OIH. We observed that the major metabolite of 4-18 F-fluorobenzoic acid is excreted rapidly and exclusively in urine as p-18 F-fluorohippurate ( 18 F-PFH) (14).…”

“…It is known that benzoic acid derivatives are converted in vivo into hippuric acid derivatives via the glycine-conjugation pathway in the liver (15,16). This observation prompted us to investigate the potential use of 18 F-PFH as a PET renal agent. We report the synthesis and initial in vivo evaluation of 18 F-PFH in a rat model.…”

“…The corresponding radiotracers included 15 O-H 2 O, 13 N-NH 3 , 82 Rb-Rb 1 , 62 CuCu(II)pyruvaldehyde bis-(N-4-methylthiosemicarbazonato), and 62 Cu-Cu(II)ethylglyoxal bis(thiosemicarbazone) for renal perfusion studies (1)(2)(3) and 68 Ga-Ga-ethylenediaminetetraacetic acid, 55 Co-Co-ethylenediaminetetraacetic acid, and 18 F-F 2 for glomerular filtration rate studies (3)(4)(5)(6)(7). In addition to drawbacks such as cost and availability, the clinical use of these radiotracers is limited by problems such as a short 2-min decay half-life ( 15 O-H 2 O) or the high affinity of 18 F-F 2 toward bone, which is less than optimal in a renal imaging study. In this scenario, PET presents almost no competitive advantage over widely used planar g-imaging for functional imaging of kidneys.…”