N-(4-(di- tert-butyl[ 18F]fluorosilyl)benzyl)-2-hydroxy-N,N-dimethylethylammonium bromide ([ 18F]SiFAN +Br −): A novel lead compound for the development of hydrophilic SiFA-based prosthetic groups for 18F-labeling (original) (raw)
Related papers
Bioconjugate Chemistry, 2009
Radiosyntheses of 18 F-radiopharmaceuticals for positron emission tomography (PET) normally require an extraordinarily high effort of technical equipment and specially trained personnel. We recently reported a novel method for the introduction of fluorine-18 into peptides for PET-imaging based on silicon-18 F-chemistry (SiFA technique). We herewith introduce the first SiFA-based Kit-like radio-fluorination of a protein (rat serum albumin, RSA) and demonstrate its usefulness for in vivo imaging with µPET in normal rats as well as in a rat heterotropic transplanted heart model. As a labeling agent, we prepared 4-(di-tert-butyl[ 18 F]fluorosilyl)benzenethiol (Si[ 18 F]FA-SH) by simple isotopic exchange in 40-60% radiochemical yield (RCY) and coupled it directly to a Sulfo-SMCC derivatized RSA in an overall RCY of 12% within 20-30 min. The technically simple labeling procedure does not require any elaborated purification procedures and is a straightforward example of a successful application of Si-18 F chemistry for in vivo imaging with PET.
Pharmaceuticals, 2021
The incorporation of silicon fluoride acceptor (SiFA) moieties into a variety of molecules, such as peptides, proteins and biologically relevant small molecules, has improved the generation of 18F-radiopharmaceuticals for medical imaging. The efficient isotopic exchange radiofluorination process, in combination with the enhanced [18F]SiFA in vivo stability, make it a suitable strategy for fluorine-18 incorporation. This review will highlight the clinical applicability of [18F]SiFA-labeled compounds and discuss the significant radiotracers currently in clinical use.
Fluorine-18 chemistry for PET: A concise introduction
2010
Fluorine-18 is the most important radionuclide used in positron emission tomography (PET) today, largely due to its attractive physical and nuclear characteristics. Agents such as the clinical oncology tracer 2-[ 18 F]fluoro-2-deoxy-Dglucose ([ 18 F]FDG), the most widely used PET-radiopharmaceutical, are driving an increasing interest in the chemistry of radiopharmaceuticals utilizing fluorine-18. This review outlines the methods for production of fluorine-18, and the development of agents for performing radiofluorination reactions. With a few exceptions, radiofluorinations can be classified as either electrophilic or nucleophilic. The electrophilic reactions mainly use molecular [ 18 F]fluorine of moderately low specific radioactivity, or reagents prepared from it, and include additions to alkenes, reactions with carbanions and especially fluorodehydrogenation and fluorodemetallation. The nucleophilic reactions usually involve no-carrier-added (highspecific-radioactivity) [ 18 F]fluoride as its K[ 18 F]F-K 222 complex and include S N 2-type substitutions in the aliphatic series and S N Ar-type substitutions in the aromatic and heteroaromatic series. Key examples from each class of radiofluorination reaction will be described, highlighting the potential of this radioisotope in the design and preparation of fluorine-18labeled probes for PET imaging.
Bioconjugate Chemistry, 2012
N-Succinimidyl 3-(di-tert-butyl[ 18 F]fluorosilyl)benzoate ([ 18 F]SiFB), a novel synthon for one-step labeling of proteins, was synthesized via a simple 18 F− 19 F isotopic exchange. A new labeling technique that circumvents the cleavage of the highly reactive active ester moiety under regular basic 18 F-labeling conditions was established. In order to synthesize high radioactivity amounts of [ 18 F]SiFB, it was crucial to partially neutralize the potassium oxalate/hydroxide that was used to elute 18 F − from the QMA cartridge with oxalic acid to prevent decomposition of the active ester moiety. Purification of [ 18 F]SiFB was performed by simple solid-phase extraction, which avoided time-consuming HPLC and yielded high specific activities of at least 525 Ci/mmol and radiochemical yields of 40−56%. In addition to conventional azeotropic drying of 18 F − in the presence of [K + ⊂2.2.2.]C 2 O 4 , a strong anion-exchange (SAX) cartridge was used to prepare anhydrous 18 F − for nucleophilic radio-fluorination omitting the vacuum assisted drying of 18 F −. Using a lyophilized mixture of [K + ⊂2.2.2.]OH resolubilized in acetonitrile, the 18 F − was eluted from the SAX cartridge and used directly for the [ 18 F]SiFB synthesis. [ 18 F]SiFB was applied to the labeling of various proteins in likeness to the most commonly used labeling synthon in protein labeling, N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]SFB). Rat serum albumin (RSA), apotransferrin, a β-cell-specific single chain antibody, and erythropoietin were successfully labeled with [ 18 F]SiFB in good radiochemical yields between 19% and 36%. [ 18 F]SiFB-and [ 18 F]SFB-derivatized RSA were directly compared as blood pool imaging agents in healthy rats using small animal positron emission tomography. Both compounds demonstrated identical biodistributions in healthy rats, accurately visualizing the blood pool with PET.
Molecules, 2011
The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D 2 -receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D 2 -receptor affinities for all compounds in the nanomolar range (K i(SiFA-DMFP) = 13.6 nM, K i(SiFA-FP) = 33.0 nM,
A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging
2011
Abstract The unnatural isotope fluorine-18 (18 F) is used as a positron emitter in molecular imaging. Currently, many potentially useful 18 F-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of 18 F requires rapid syntheses for which [18 F] fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment.
Late stage 18F‐difluoromethyl labeling of N‐heteroaromatics with high molar activity for PET imaging
Angewandte Chemie
Despite ag rowing interest in CHF 2 in medicinal chemistry,there is alackofefficient methods for the insertion of CHF 18 Fi nto druglike compounds.H erein described is ap hotoredoxf lowr eaction for 18 F-difluoromethylation of Nheteroaromatics that are widely used in medicinal chemistry. Following the two-step synthesis for anew 18 F-difluoromethylation reagent, the photoredoxreaction is completed within two minutes and proceeds by CÀHa ctivation, circumventing the need for pre-functionalizationo ft he substrate.T he method is operationally simple and affords straightforwarda ccess to radiolabeled N-heteroaromatics with high molar activity suitable for biological in vivo studies and clinical application.