The Radiopharmaceutical Chemistry of Fluorine-18: Nucleophilic Fluorinations

Ermert, Johannes

doi:10.1007/978-3-319-98947-1_15

Cited by 8 publications

(9 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many synthetic challenges limited the use of electrophilic radiofluorination, and automated synthesis modules (54). The nucleophilic radiofluorination reactions with 18 F fluoride are most common since the radiochemical yield is >90% due to direct insertion of fluorine-18 into precursor, leakage or contamination is very limited as 18 F fluoride comes as a liquid from the cyclotron, achieve maximum molar activity (500-5,500 GBq/µmol), and 18 F fluoride is a selective nucleophilic agent for regiospecific reactions (55). The major limitation of 18 F fluoride is ready to form hydrogen bonds with the 18 O water and reduces the nucleophilic substitution reaction rate due to its nucleophilicity, but it can be achieved by removal of water by evaporation and use of polar aprotic solvents in radiochemical reactions (56).…”

Section: The Chemistry Of Radiolabeling With Fluorine-18 and Carbon-1...mentioning

confidence: 99%

PET Molecular Imaging in Drug Development: The Imaging and Chemistry Perspective

et al. 2022

View full text Add to dashboard Cite

Positron emission tomography with selective radioligands advances the drug discovery and development process by revealing information about target engagement, proof of mechanism, pharmacokinetic and pharmacodynamic profiles. Positron emission tomography (PET) is an essential and highly significant tool to study therapeutic drug development, dose regimen, and the drug plasma concentrations of new drug candidates. Selective radioligands bring up target-specific information in several disease states including cancer, cardiovascular, and neurological conditions by quantifying various rates of biological processes with PET, which are associated with its physiological changes in living subjects, thus it reveals disease progression and also advances the clinical investigation. This study explores the major roles, applications, and advances of PET molecular imaging in drug discovery and development process with a wide range of radiochemistry as well as clinical outcomes of positron-emitting carbon-11 and fluorine-18 radiotracers.

show abstract

Section: The Chemistry Of Radiolabeling With Fluorine-18 and Carbon-1...mentioning

confidence: 99%

PET Molecular Imaging in Drug Development: The Imaging and Chemistry Perspective

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Whereas, chelated radionuclides typically possess similar moieties regardless of the metal to be chelated, covalent attachment of radionuclides usually requires the generation of a variety of precursors, depending on the radionuclide to be attached. In the case of carbon-11, which is typically added as the electrophilic [ 11 C]methyl iodide, the precursor must be sufficiently nucleophilic [24]; whereas, in the case of [ 18 F], the precursor is usually an electrophile to allow for the addition of the nucleophilic [ 18 F]fluoride anions [25]. In the case of the other halogens, Br or I, this typically proceeds via nucleophilic aromatic substitution of tributyltin (SnBu 3 ) derivative [21,26].…”

Section: Radionuclide Choice: Chelation Vs Covalent Attachmentmentioning

confidence: 99%

“…Fluorine-18 is the most widely used positron-emitting radionuclide for imaging [25], usually in the form of [ 18 F]fluorodeoxyglucose ([ 18 F]FDG). Fluorine-18 has a t 1/2 of 110 min, making it much more useful from a clinical imaging perspective than carbon-11 because it can be shipped over short distances allowing wider access and improved biodistribution/pharmacokinetic characteristics.…”

Section: Radionuclide Choice: Chelation Vs Covalent Attachmentmentioning

confidence: 99%

Radiochemical Approaches to Imaging Bacterial Infections: Intracellular versus Extracellular Targets

Northrup

Mach

Sellmyer

2019

IJMS

View full text Add to dashboard Cite

The discovery of penicillin began the age of antibiotics, which was a turning point in human healthcare. However, to this day, microbial infections are still a concern throughout the world, and the rise of multidrug-resistant organisms is an increasing challenge. To combat this threat, diagnostic imaging tools could be used to verify the causative organism and curb inappropriate use of antimicrobial drugs. Nuclear imaging offers the sensitivity needed to detect small numbers of bacteria in situ. Among nuclear imaging tools, radiolabeled antibiotics traditionally have lacked the sensitivity or specificity necessary to diagnose bacterial infections accurately. One reason for the lack of success is that the antibiotics were often chelated to a radiometal. This was done without addressing the ramifications of how the radiolabeling would impact probe entry to the bacterial cell, or the mechanism of binding to an intracellular target. In this review, we approach bacterial infection imaging through the lens of bacterial specific molecular targets, their intracellular or extracellular location, and discuss radiochemistry strategies to guide future probe development.

show abstract

“…The high resolution and sensitivity of PET allow the detection of changes in cellular function or receptor densities during disease development using molecular tracers, most frequently labeled with fluorine-18. Radiolabeled biological and pharmaceutical active molecules carrying 18 F are of increasing importance for preclinical, clinical, and nuclear medical research due to the unique properties of 18 F, such as low β + -energy, long half-life (109.77 min), and the easy accessibility of no-carrier-added [ 18 F]fluoride [2]. The nuclear reaction of 18 O(p,n) 18 F in a small-scale cyclotron is the commonly applied process for the production of [ 18 F]fluoride, which involves the bombardment of H 2 [ 18 O]O with highly accelerated protons, and is the basis of the supply of radiopharmaceutical facilities.…”

Section: Introductionmentioning

confidence: 99%

“…1 Unless noted otherwise, all reactions were carried out using 15.0 µ mol of K2CO3 (1 M, 15 µ L) and 39.0 µ mol of PTC at 85 °C for 20 min 2. Radio-thin layered silica gel chromatography (radio-TLC) plates were run with EtOAc mobile phase; the shown values are the mean of three determinations.…”

mentioning

confidence: 99%

18F-Fluorination Using Tri-Tert-Butanol Ammonium Iodide as Phase-Transfer Catalyst: An Alternative Minimalist Approach

et al. 2021

View full text Add to dashboard Cite

The 18F syntheses of tracers for positron emission tomography (PET) typically require several steps, including extraction of [18F]fluoride from H2[18O]O, elution, and drying, prior to nucleophilic substitution reaction, being a laborious and time-consuming process. The elution of [18F]fluoride is commonly achieved by phase transfer catalysts (PTC) in aqueous solution, which makes azeotropic drying indispensable. The ideal PTC is characterized by a slightly basic nature, its capacity to elute [18F]fluoride with anhydrous solvents, and its efficient complex formation with [18F]fluoride during subsequent labeling. Herein, we developed tri-(tert-butanol)-methylammonium iodide (TBMA-I), a quaternary ammonium salt serving as the PTC for 18F-fluorination reactions. The favorable elution efficiency of [18F]fluoride using TBMA-I was demonstrated with aprotic and protic solvents, maintaining high 18F-recoveries of 96–99%. 18F-labeling reactions using TBMA-I as PTC were studied with aliphatic 1,3-ditosylpropane and aryl pinacol boronate esters as precursors, providing 18F-labeled products in moderate-to-high radiochemical yields. TBMA-I revealed adequate properties for application to 18F-fluorination reactions and could be used for elution of [18F]fluoride with MeOH, omitting an additional base and azeotropic drying prior to 18F-labeling. We speculate that the tert-alcohol functionality of TBMA-I promotes intermolecular hydrogen bonding, which enhances the elution efficiency and stability of [18F]fluoride during nucleophilic 18F-fluorination.

show abstract

The Radiopharmaceutical Chemistry of Fluorine-18: Nucleophilic Fluorinations

Cited by 8 publications

References 49 publications

PET Molecular Imaging in Drug Development: The Imaging and Chemistry Perspective

PET Molecular Imaging in Drug Development: The Imaging and Chemistry Perspective

Radiochemical Approaches to Imaging Bacterial Infections: Intracellular versus Extracellular Targets

18F-Fluorination Using Tri-Tert-Butanol Ammonium Iodide as Phase-Transfer Catalyst: An Alternative Minimalist Approach

Contact Info

Product

Resources

About